Péter Degrell - Academia.edu (original) (raw)
Papers by Péter Degrell
Orvosi Hetilap, Dec 1, 2011
IgA nephropathy is the most common primary glomerulonephritis worldwide. The clinical spectrum co... more IgA nephropathy is the most common primary glomerulonephritis worldwide. The clinical spectrum covers a wide range of features from minor urinary abnormalities (asymptomatic hematuria and mild proteinuria with normal renal function) to acute and chronic renal insufficiency. Ideally, the goal of treatment would be to correct any defects in IgA1 glycosylation and to modify mesangial deposition or removal of IgA1 deposits. There are only a few randomized controlled trials in IgA nephropathy; for this reason most treatment options are largely based on expert opinion. Authors discuss therapeutic options of different clinical pictures and the optimized renoprotective treatment of all IgA nephropathy patients. Orv. Hetil., 2011, 152, 2039–2046.
Orvosi Hetilap, Dec 18, 2011
IgA nephropathy is the most common primary glomerulonephritis worldwide. The clinical spectrum co... more IgA nephropathy is the most common primary glomerulonephritis worldwide. The clinical spectrum covers a wide range of features from minor urinary abnormalities (asymptomatic hematuria and mild proteinuria with normal renal function) to acute and chronic renal insufficiency. Ideally, the goal of treatment would be to correct any defects in IgA1 glycosylation and to modify mesangial deposition or removal of IgA1 deposits. There are only a few randomized controlled trials in IgA nephropathy; for this reason most treatment options are largely based on expert opinion. Authors discuss therapeutic options of different clinical pictures and the optimized renoprotective treatment of all IgA nephropathy patients.
Journal of Nephrology, 2011
Orvosi Hetilap, Mar 1, 2007
The authors review the case of a 30 years old female patient presenting with a 48 hours-standing ... more The authors review the case of a 30 years old female patient presenting with a 48 hours-standing anuria, who permanently used products of grist of a virtuous plant, Guarana and occasionally used a parenteral non-steroid painkiller. The clinical history and laboratory results showed acute renal and hepatic failure. The histological picture of the renal biopsy specimen verified an acute tubular necrosis. After temporary dialysis treatment, her renal function recovered progressively with compensatory polyuria. The authors would like to draw the attention to the risks of the use of over-the-counter marketed paramedicinal products—per se or in combination with pharmaceutically registered products—sold in pharmacies and nutrition supplement stores.
Orvosi Hetilap, Feb 1, 2008
Focal segmental glomerulosclerosis is a glomerular injury with typical morphology detectable by l... more Focal segmental glomerulosclerosis is a glomerular injury with typical morphology detectable by light microscopy. It has different histological subtypes and clinical symptoms. These different subtypes were recently systematized (Columbia classification). Focal segmental glomerulosclerosis is considered as the major type of podocytopathies, because podocytes are affected at each type of glomerular injury. Besides the primary forms of focal segmental glomerulosclerosis, an increased number of the secondary types are recognized. The wide use of drugs for renal protection in general and the long term administration of steroid therapy in some primary (idiopathic) cases are new elements among the therapeutic possibilities.
LAM (Lege Artis Medicinæ), 2003
International Urology and Nephrology, Sep 3, 2014
those patients who underwent tonsillectomy (Group II) versus patients without tonsillectomy (Grou... more those patients who underwent tonsillectomy (Group II) versus patients without tonsillectomy (Group I) (p < 0.001 and p = 0.005). The mean renal survival time was significantly longer for both end-points between those patients who had macrohaematuric episodes versus patients who had no macrohaematuric episodes (p = 0.035 and p = 0.019). Tonsillectomy, baseline eGFR and 24-h proteinuria were independent risk factors for both renal end-points. Conclusion Tonsillectomy may delay the progression of IgA nephropathy mainly in IgA nephropathy patients with macrohaematuria. Prospective investigation of the protective role of tonsillectomy in Caucasian patients is needed. Keywords IgA nephropathy • Progression of IgA nephropathy • Tonsillectomy Pathologically, IgAN is characterised by the glomerular deposition of polymeric IgA1 mainly in the mesangium. In patients with IgAN, circulating as well as glomerular IgA1 molecules have an aberrant structure of O-glycans [6-8].
Journal of Molecular Neuroscience, 2018
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that exerts general ... more Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that exerts general cytoprotective effects, including protection in different kidney disorders. The aim of our study was to investigate the ischemia/reperfusioninduced kidney injury of male and female rats to confirm the protective effects of PACAP in the kidney and to reveal possible gender differences. Male and female Wistar rats underwent unilateral renal artery clamping followed by 24-h, 48-h, or 14-day reperfusion. PACAP was administered intravenously before arterial clamping in half of the rats. Tubular damage, cytokine expression pattern, oxidative stress marker, antioxidative status and signaling pathways were evaluated using histology, immunohistology, cytokine array, PCR, and Western blot. Tubular damage was significantly less severe in the PACAPtreated male and female rats compared to controls. Results of female animals were significantly better in both treated and untreated groups. Cytokine expression, oxidative stress marker and antioxidative status confirmed the histological results. We also revealed that PACAP counteracted the decreased PKA phosphorylation, influenced the expression of BMP2 and BMP4, and increased the expression of the protein Smad1. We conclude that PACAP is protective in ischemia/reperfusion-induced kidney injury in both sexes, but females had markedly less pronounced injury after ischemia/reperfusion, possibly also involving further protective factors, the investigation of which could have future therapeutic value in treating ischemic kidney injuries.
Pathology & Oncology Research, Dec 1, 2000
Clinical hemorheology and microcirculation, 2012
We studied the protective effects of postconditioning (PS) in healthy and hypercholesterolemic ra... more We studied the protective effects of postconditioning (PS) in healthy and hypercholesterolemic rats after renal ischaemia-reperfusion (IR) injury. We aimed to examine cytokine expression and apoptosis in tissue damage after revascularisation (TNF-α levels in serum and tissue). Male Wistar rats (n = 32) were divided into four groups. The animals of normal feed groups (NF) were fed with normal rat chow and the cholesterol feed groups (CF) were fed with 1.5% cholesterol containing diet for 8 weeks. Anaesthetized rats underwent a 45-min cross-clamping in both kidney pedicles. Ischaemia was followed by 120-min reperfusion with or without PS protocol (group PS vs. IR). Postconditioning was induced by four intermittent periods of ischaemia-reperfusion of 15-s duration each. Serum cholesterol, triglyceride, urea and creatinine levels were determined. Proinflammation was characterized by the measurement of serum TNF-α. Tissue injury in kidney was determined by formaline-fixed, paraffin-embed...
Nephron Experimental Nephrology, 2008
Background: In glomerulonephritides, dysmorphic red blood cells (RBCs) with membrane blebs can be... more Background: In glomerulonephritides, dysmorphic red blood cells (RBCs) with membrane blebs can be found in the urine; this is referred to as glomerular hematuria. Glomerulonephritides are characterized by increased carbonyl stress and elevated methylglyoxal (MGO) levels. MGO causes oxidative stress and intracellular calcium accumulation. In the present study, we investigated whether the effect of MGO-induced calcium accumulation in RBCs develops through increased oxidative stress. Furthermore, we studied whether MGO can lead to RBC membrane blebbing. Methods: RBC suspensions from healthy volunteers were incubated with different concentrations of MGO at 37°C. We measured oxidative stress and intracellular calcium level using fluorescent indicators. We determined the frequency of dysmorphic RBCs, and also performed scanning electron microscopy. Results: MGO increased oxidative stress and caused accumulation of calcium in isolated RBCs. These effects could be prevented using antioxidan...
Endothelium, 2002
Bradykinin-induced increase in the intracellular concentration of free calcium evokes an activati... more Bradykinin-induced increase in the intracellular concentration of free calcium evokes an activation of the endothelial nitric oxide synthase (eNOS) enzyme, producing nitric oxide (NO). Cigarette smoke inhibits the eNOS-NO-cGMP signaling pathway. The pathomechanism of this deleterious effect of smoke on NO production is unknown. The aim of this study was to investigate the effect of gas phase smoke trapped in a buffer (smoke buffer, SB) on the bradykinin-induced calcium increase in cultured endothelial cells. FURA-2-AM was used to detect bradykinin-induced calcium increase. A sensitive, fluorescent method using O-phthaldialdehyde was used for the determination of intracellular reduced glutathione (GSH) and protein-thiol levels. SB caused a time- and concentration-dependent inhibition of bradykinin-induced calcium increase. Formaldehyde, a component of SB, inhibited bradykinin-induced calcium increase in concentrations characteristic for SB. SB decreased both the intracellular GSH (0.22 +/- 0.06 vs. 2.23 +/- 0.32 mumol/g protein, SB vs. control, p < .001) and protein-thiol levels (4.98 +/- 0.54 vs. 7.31 +/- 0.97 microEqu GSH/g protein, SB vs. control, p < .05) in the endothelial cells. Intracellular GSH and protein-thiol levels were not changed by 80 microM formaldehyde. GSH (4 mM) prevented the effect of SB (p < .001) and formaldehyde (p < .05) on the bradykinin-induced calcium increase. Our data support the premise that SB inhibits bradykinin-induced calcium increase. This inhibition is partially due to protein-thiol oxidation but may also be caused by the formaldehyde content of SB, which inhibits calcium increase in a protein-thiol-independent manner.
Cellular Physiology and Biochemistry, 2011
Several studies reported sexual dimorphism in the signaling mechanisms of renal ischemia/reperfus... more Several studies reported sexual dimorphism in the signaling mechanisms of renal ischemia/reperfusion (I/R). The anti-apoptotic serum and glucocorticoidregulated kinase-1 (SGK-1) is up-regulated and has a significant protective role in renal I/R. SGK-1 has several target molecules, and inhibition of the inducible nitric oxide synthase (iNOS) transcription is one of its effector mechanisms. The objective of the present study was to examine if there is a genderspecific expression and activation of SGK-1 during renal I/R injury. In vitro, treatment of HK-2 kidney proximal tubular cells with different concentrations of 17-beta estradiol had no effect, whereas testosterone increased SGK-1 abundance in a dose-dependent manner. In vivo, in a rat model of unilateral renal I/R injury, there was a higher SGK-1 expression and phosphorylation in males 2 and 24 h after ischemia paralleled by reduction in the mRNA expression of iNOS compared to females. Deprivation of testosterone by castration of males resulted in decreased SGK-1 protein level at all time-points and reduced phosphorylation 2 and 24 h after reperfusion. Our results suggest that testosterone up-regulates SGK-1 in the kidney contributing to sexual dimorphisms in the cell signalling machinery. The significance of the testosterone-regulated SGK-1 level and activity in the kidney needs further investigations.
PLoS ONE, 2012
Angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) are th... more Angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) are the standard clinical therapy of diabetic nephropathy (DN), while aldosterone antagonists are only used as adjuncts. Previously in experimental DN we showed that Na/K ATPase (NKA) is mislocated and angiotensin II leads to superimposed renal progression. Here we investigated the monotherapeutic effect of aldosterone blockers on the progression of DN and renal NKA alteration in comparison to ACEi and ARBs. Streptozotocin-diabetic rats developing DN were treated with aldosterone antagonists; ACEi and ARB. Renal function, morphology, protein level and tubular localization of NKA were analyzed. To evaluate the effect of high glucose per se; HK-2 proximal tubular cells were cultured in normal or high concentration of glucose and treated with the same agents. Aldosterone antagonists were the most effective in ameliorating functional and structural kidney damage and they normalized diabetes induced bradycardia and weight loss. Aldosterone blockers also prevented hyperglycemia and diabetes induced increase in NKA protein level and enzyme mislocation. A monotherapy with aldosterone antagonists might be as, or more effective than ACEi or ARBs in the prevention of STZ-induced DN. Furthermore the alteration of the NKA could represent a novel pathophysiological feature of DN and might serve as an additional target of aldosterone blockers.
Journal of Molecular Neuroscience, 2014
• Check the metadata sheet to make sure that the header information, especially author names and ... more • Check the metadata sheet to make sure that the header information, especially author names and the corresponding affiliations are correctly shown. • Check the questions that may have arisen during copy editing and insert your answers/corrections. • Check that the text is complete and that all figures, tables and their legends are included. Also check the accuracy of special characters, equations, and electronic supplementary material if applicable. If necessary refer to the Edited manuscript. • The publication of inaccurate data such as dosages and units can have serious consequences. Please take particular care that all such details are correct. • Please do not make changes that involve only matters of style. We have generally introduced forms that follow the journal's style. Substantial changes in content, e.g., new results, corrected values, title and authorship are not allowed without the approval of the responsible editor. In such a case, please contact the Editorial Office and return his/her consent together with the proof. • If we do not receive your corrections within 48 hours, we will send you a reminder. Please note Your article will be published Online First approximately one week after receipt of your corrected proofs. This is the official first publication citable with the DOI. Further changes are, therefore, not possible.
The Journal of Physiology, 2008
Angiotensin II (ANGII) plays a central role in the enhanced sodium reabsorption in early type 1 d... more Angiotensin II (ANGII) plays a central role in the enhanced sodium reabsorption in early type 1 diabetes in man and in streptozotocin-induced (STZ) diabetic rats. This study investigates the effect of untreated STZ-diabetes leading to diabetic nephropathy in combination with ANGII treatment, on the abundance and localization of the renal Na + ,K +-ATPase (NKA), a major contributor of renal sodium handling. After 7 weeks of STZ-diabetes (i.v. 65 mg kg −1) a subgroup of control (C) and diabetic (D7) Wistar rats were treated with ANGII (s.c. minipump 33 μg kg −1 h −1 for 24 h; CA and D7A). We measured renal function and mRNA expression, protein level, Serin23 phosphorylation, subcellular distribution, and enzyme activity of NKA α-1 subunit in the kidney cortex. Diabetes increased serum creatinine and urea nitrogen levels (C versus D7), as did ANGII (C versus CA, D7 versus D7A). Both diabetes (C versus D7) and ANGII increased NKA α-1 protein level and enzyme activity (C versus CA, D7 versus D7A). Furthermore, the combination led to an additive increase (D7 versus D7A, CA versus D7A). NKA α-1 Ser23 phosphorylation was higher both in D7 and ANGII-treated rats in the non-cytoskeletal fraction, while no signal was detected in the cytoskeletal fraction. Control kidneys showed NKA α-1 immunopositivity on the basolateral membrane of proximal tubular cells, while both D7 and ANGII broadened NKA immunopositivity towards the cytoplasm. Our study demonstrates that diabetes mellitus (DM) increases the mRNA expression, protein level, Ser23 phosphorylation and enzyme activity of renal NKA, which is further elevated by ANGII. Despite an increase in total NKA quantity in diabetic nephropathy, the redistribution to the cystosol suggests the Na + pump is no longer functional. ANGII also caused translocation from the basolateral membrane, thus in diabetic states where ANGII level is acutely elevated, the loss of NKA will be exacerbated. This provides another mechanism by which ANGII blockade is likely to be protective.
Az ACE es a glutation peroxidaz gen polimorfizmusa osszefuggest mutat a metabolikus szindroma sul... more Az ACE es a glutation peroxidaz gen polimorfizmusa osszefuggest mutat a metabolikus szindroma sulyossagaval, es az oxidativ stressz mertekevel. A karbonil stressz egyik forrasakent ismert dohanyfust a metabolikus szindroma pathogeneziseben fontos szerepet jatszo endothel funkciot karositja. Az agyat ert karbonil stressz metabolikus szindromara jellegzetes klinikai kep kialakulasahoz vezet. A metabolikus szindromas allatok vesejeben a karbonil stressz vegtermekei es a renin kolokalizaciot mutat. Izolalt vorosvertestekben a karbonil stressz fokozott oxidativ stresszt okoz. A karbonil-stresszel jaro diabeteszes glukozuria a vese tubularis sejtjeiben hidroxil szabadgyok- termeleshez vezet. Az oxidativ stressz fontos szerepet jatszik a diabeteszes cataracta, a diabeteszes mikroalbuminuria kialakulasaban es merteke osszefugg a diabeteszes erkarosodas mertekevel. A karbonil es oxidativ stressz hatasara kepződő glikacios vegtermekek szintje a halalozas fuggetlen prediktora. Diabeteszes bete...
Orvosi Hetilap, Dec 1, 2011
IgA nephropathy is the most common primary glomerulonephritis worldwide. The clinical spectrum co... more IgA nephropathy is the most common primary glomerulonephritis worldwide. The clinical spectrum covers a wide range of features from minor urinary abnormalities (asymptomatic hematuria and mild proteinuria with normal renal function) to acute and chronic renal insufficiency. Ideally, the goal of treatment would be to correct any defects in IgA1 glycosylation and to modify mesangial deposition or removal of IgA1 deposits. There are only a few randomized controlled trials in IgA nephropathy; for this reason most treatment options are largely based on expert opinion. Authors discuss therapeutic options of different clinical pictures and the optimized renoprotective treatment of all IgA nephropathy patients. Orv. Hetil., 2011, 152, 2039–2046.
Orvosi Hetilap, Dec 18, 2011
IgA nephropathy is the most common primary glomerulonephritis worldwide. The clinical spectrum co... more IgA nephropathy is the most common primary glomerulonephritis worldwide. The clinical spectrum covers a wide range of features from minor urinary abnormalities (asymptomatic hematuria and mild proteinuria with normal renal function) to acute and chronic renal insufficiency. Ideally, the goal of treatment would be to correct any defects in IgA1 glycosylation and to modify mesangial deposition or removal of IgA1 deposits. There are only a few randomized controlled trials in IgA nephropathy; for this reason most treatment options are largely based on expert opinion. Authors discuss therapeutic options of different clinical pictures and the optimized renoprotective treatment of all IgA nephropathy patients.
Journal of Nephrology, 2011
Orvosi Hetilap, Mar 1, 2007
The authors review the case of a 30 years old female patient presenting with a 48 hours-standing ... more The authors review the case of a 30 years old female patient presenting with a 48 hours-standing anuria, who permanently used products of grist of a virtuous plant, Guarana and occasionally used a parenteral non-steroid painkiller. The clinical history and laboratory results showed acute renal and hepatic failure. The histological picture of the renal biopsy specimen verified an acute tubular necrosis. After temporary dialysis treatment, her renal function recovered progressively with compensatory polyuria. The authors would like to draw the attention to the risks of the use of over-the-counter marketed paramedicinal products—per se or in combination with pharmaceutically registered products—sold in pharmacies and nutrition supplement stores.
Orvosi Hetilap, Feb 1, 2008
Focal segmental glomerulosclerosis is a glomerular injury with typical morphology detectable by l... more Focal segmental glomerulosclerosis is a glomerular injury with typical morphology detectable by light microscopy. It has different histological subtypes and clinical symptoms. These different subtypes were recently systematized (Columbia classification). Focal segmental glomerulosclerosis is considered as the major type of podocytopathies, because podocytes are affected at each type of glomerular injury. Besides the primary forms of focal segmental glomerulosclerosis, an increased number of the secondary types are recognized. The wide use of drugs for renal protection in general and the long term administration of steroid therapy in some primary (idiopathic) cases are new elements among the therapeutic possibilities.
LAM (Lege Artis Medicinæ), 2003
International Urology and Nephrology, Sep 3, 2014
those patients who underwent tonsillectomy (Group II) versus patients without tonsillectomy (Grou... more those patients who underwent tonsillectomy (Group II) versus patients without tonsillectomy (Group I) (p < 0.001 and p = 0.005). The mean renal survival time was significantly longer for both end-points between those patients who had macrohaematuric episodes versus patients who had no macrohaematuric episodes (p = 0.035 and p = 0.019). Tonsillectomy, baseline eGFR and 24-h proteinuria were independent risk factors for both renal end-points. Conclusion Tonsillectomy may delay the progression of IgA nephropathy mainly in IgA nephropathy patients with macrohaematuria. Prospective investigation of the protective role of tonsillectomy in Caucasian patients is needed. Keywords IgA nephropathy • Progression of IgA nephropathy • Tonsillectomy Pathologically, IgAN is characterised by the glomerular deposition of polymeric IgA1 mainly in the mesangium. In patients with IgAN, circulating as well as glomerular IgA1 molecules have an aberrant structure of O-glycans [6-8].
Journal of Molecular Neuroscience, 2018
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that exerts general ... more Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that exerts general cytoprotective effects, including protection in different kidney disorders. The aim of our study was to investigate the ischemia/reperfusioninduced kidney injury of male and female rats to confirm the protective effects of PACAP in the kidney and to reveal possible gender differences. Male and female Wistar rats underwent unilateral renal artery clamping followed by 24-h, 48-h, or 14-day reperfusion. PACAP was administered intravenously before arterial clamping in half of the rats. Tubular damage, cytokine expression pattern, oxidative stress marker, antioxidative status and signaling pathways were evaluated using histology, immunohistology, cytokine array, PCR, and Western blot. Tubular damage was significantly less severe in the PACAPtreated male and female rats compared to controls. Results of female animals were significantly better in both treated and untreated groups. Cytokine expression, oxidative stress marker and antioxidative status confirmed the histological results. We also revealed that PACAP counteracted the decreased PKA phosphorylation, influenced the expression of BMP2 and BMP4, and increased the expression of the protein Smad1. We conclude that PACAP is protective in ischemia/reperfusion-induced kidney injury in both sexes, but females had markedly less pronounced injury after ischemia/reperfusion, possibly also involving further protective factors, the investigation of which could have future therapeutic value in treating ischemic kidney injuries.
Pathology & Oncology Research, Dec 1, 2000
Clinical hemorheology and microcirculation, 2012
We studied the protective effects of postconditioning (PS) in healthy and hypercholesterolemic ra... more We studied the protective effects of postconditioning (PS) in healthy and hypercholesterolemic rats after renal ischaemia-reperfusion (IR) injury. We aimed to examine cytokine expression and apoptosis in tissue damage after revascularisation (TNF-α levels in serum and tissue). Male Wistar rats (n = 32) were divided into four groups. The animals of normal feed groups (NF) were fed with normal rat chow and the cholesterol feed groups (CF) were fed with 1.5% cholesterol containing diet for 8 weeks. Anaesthetized rats underwent a 45-min cross-clamping in both kidney pedicles. Ischaemia was followed by 120-min reperfusion with or without PS protocol (group PS vs. IR). Postconditioning was induced by four intermittent periods of ischaemia-reperfusion of 15-s duration each. Serum cholesterol, triglyceride, urea and creatinine levels were determined. Proinflammation was characterized by the measurement of serum TNF-α. Tissue injury in kidney was determined by formaline-fixed, paraffin-embed...
Nephron Experimental Nephrology, 2008
Background: In glomerulonephritides, dysmorphic red blood cells (RBCs) with membrane blebs can be... more Background: In glomerulonephritides, dysmorphic red blood cells (RBCs) with membrane blebs can be found in the urine; this is referred to as glomerular hematuria. Glomerulonephritides are characterized by increased carbonyl stress and elevated methylglyoxal (MGO) levels. MGO causes oxidative stress and intracellular calcium accumulation. In the present study, we investigated whether the effect of MGO-induced calcium accumulation in RBCs develops through increased oxidative stress. Furthermore, we studied whether MGO can lead to RBC membrane blebbing. Methods: RBC suspensions from healthy volunteers were incubated with different concentrations of MGO at 37°C. We measured oxidative stress and intracellular calcium level using fluorescent indicators. We determined the frequency of dysmorphic RBCs, and also performed scanning electron microscopy. Results: MGO increased oxidative stress and caused accumulation of calcium in isolated RBCs. These effects could be prevented using antioxidan...
Endothelium, 2002
Bradykinin-induced increase in the intracellular concentration of free calcium evokes an activati... more Bradykinin-induced increase in the intracellular concentration of free calcium evokes an activation of the endothelial nitric oxide synthase (eNOS) enzyme, producing nitric oxide (NO). Cigarette smoke inhibits the eNOS-NO-cGMP signaling pathway. The pathomechanism of this deleterious effect of smoke on NO production is unknown. The aim of this study was to investigate the effect of gas phase smoke trapped in a buffer (smoke buffer, SB) on the bradykinin-induced calcium increase in cultured endothelial cells. FURA-2-AM was used to detect bradykinin-induced calcium increase. A sensitive, fluorescent method using O-phthaldialdehyde was used for the determination of intracellular reduced glutathione (GSH) and protein-thiol levels. SB caused a time- and concentration-dependent inhibition of bradykinin-induced calcium increase. Formaldehyde, a component of SB, inhibited bradykinin-induced calcium increase in concentrations characteristic for SB. SB decreased both the intracellular GSH (0.22 +/- 0.06 vs. 2.23 +/- 0.32 mumol/g protein, SB vs. control, p < .001) and protein-thiol levels (4.98 +/- 0.54 vs. 7.31 +/- 0.97 microEqu GSH/g protein, SB vs. control, p < .05) in the endothelial cells. Intracellular GSH and protein-thiol levels were not changed by 80 microM formaldehyde. GSH (4 mM) prevented the effect of SB (p < .001) and formaldehyde (p < .05) on the bradykinin-induced calcium increase. Our data support the premise that SB inhibits bradykinin-induced calcium increase. This inhibition is partially due to protein-thiol oxidation but may also be caused by the formaldehyde content of SB, which inhibits calcium increase in a protein-thiol-independent manner.
Cellular Physiology and Biochemistry, 2011
Several studies reported sexual dimorphism in the signaling mechanisms of renal ischemia/reperfus... more Several studies reported sexual dimorphism in the signaling mechanisms of renal ischemia/reperfusion (I/R). The anti-apoptotic serum and glucocorticoidregulated kinase-1 (SGK-1) is up-regulated and has a significant protective role in renal I/R. SGK-1 has several target molecules, and inhibition of the inducible nitric oxide synthase (iNOS) transcription is one of its effector mechanisms. The objective of the present study was to examine if there is a genderspecific expression and activation of SGK-1 during renal I/R injury. In vitro, treatment of HK-2 kidney proximal tubular cells with different concentrations of 17-beta estradiol had no effect, whereas testosterone increased SGK-1 abundance in a dose-dependent manner. In vivo, in a rat model of unilateral renal I/R injury, there was a higher SGK-1 expression and phosphorylation in males 2 and 24 h after ischemia paralleled by reduction in the mRNA expression of iNOS compared to females. Deprivation of testosterone by castration of males resulted in decreased SGK-1 protein level at all time-points and reduced phosphorylation 2 and 24 h after reperfusion. Our results suggest that testosterone up-regulates SGK-1 in the kidney contributing to sexual dimorphisms in the cell signalling machinery. The significance of the testosterone-regulated SGK-1 level and activity in the kidney needs further investigations.
PLoS ONE, 2012
Angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) are th... more Angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) are the standard clinical therapy of diabetic nephropathy (DN), while aldosterone antagonists are only used as adjuncts. Previously in experimental DN we showed that Na/K ATPase (NKA) is mislocated and angiotensin II leads to superimposed renal progression. Here we investigated the monotherapeutic effect of aldosterone blockers on the progression of DN and renal NKA alteration in comparison to ACEi and ARBs. Streptozotocin-diabetic rats developing DN were treated with aldosterone antagonists; ACEi and ARB. Renal function, morphology, protein level and tubular localization of NKA were analyzed. To evaluate the effect of high glucose per se; HK-2 proximal tubular cells were cultured in normal or high concentration of glucose and treated with the same agents. Aldosterone antagonists were the most effective in ameliorating functional and structural kidney damage and they normalized diabetes induced bradycardia and weight loss. Aldosterone blockers also prevented hyperglycemia and diabetes induced increase in NKA protein level and enzyme mislocation. A monotherapy with aldosterone antagonists might be as, or more effective than ACEi or ARBs in the prevention of STZ-induced DN. Furthermore the alteration of the NKA could represent a novel pathophysiological feature of DN and might serve as an additional target of aldosterone blockers.
Journal of Molecular Neuroscience, 2014
• Check the metadata sheet to make sure that the header information, especially author names and ... more • Check the metadata sheet to make sure that the header information, especially author names and the corresponding affiliations are correctly shown. • Check the questions that may have arisen during copy editing and insert your answers/corrections. • Check that the text is complete and that all figures, tables and their legends are included. Also check the accuracy of special characters, equations, and electronic supplementary material if applicable. If necessary refer to the Edited manuscript. • The publication of inaccurate data such as dosages and units can have serious consequences. Please take particular care that all such details are correct. • Please do not make changes that involve only matters of style. We have generally introduced forms that follow the journal's style. Substantial changes in content, e.g., new results, corrected values, title and authorship are not allowed without the approval of the responsible editor. In such a case, please contact the Editorial Office and return his/her consent together with the proof. • If we do not receive your corrections within 48 hours, we will send you a reminder. Please note Your article will be published Online First approximately one week after receipt of your corrected proofs. This is the official first publication citable with the DOI. Further changes are, therefore, not possible.
The Journal of Physiology, 2008
Angiotensin II (ANGII) plays a central role in the enhanced sodium reabsorption in early type 1 d... more Angiotensin II (ANGII) plays a central role in the enhanced sodium reabsorption in early type 1 diabetes in man and in streptozotocin-induced (STZ) diabetic rats. This study investigates the effect of untreated STZ-diabetes leading to diabetic nephropathy in combination with ANGII treatment, on the abundance and localization of the renal Na + ,K +-ATPase (NKA), a major contributor of renal sodium handling. After 7 weeks of STZ-diabetes (i.v. 65 mg kg −1) a subgroup of control (C) and diabetic (D7) Wistar rats were treated with ANGII (s.c. minipump 33 μg kg −1 h −1 for 24 h; CA and D7A). We measured renal function and mRNA expression, protein level, Serin23 phosphorylation, subcellular distribution, and enzyme activity of NKA α-1 subunit in the kidney cortex. Diabetes increased serum creatinine and urea nitrogen levels (C versus D7), as did ANGII (C versus CA, D7 versus D7A). Both diabetes (C versus D7) and ANGII increased NKA α-1 protein level and enzyme activity (C versus CA, D7 versus D7A). Furthermore, the combination led to an additive increase (D7 versus D7A, CA versus D7A). NKA α-1 Ser23 phosphorylation was higher both in D7 and ANGII-treated rats in the non-cytoskeletal fraction, while no signal was detected in the cytoskeletal fraction. Control kidneys showed NKA α-1 immunopositivity on the basolateral membrane of proximal tubular cells, while both D7 and ANGII broadened NKA immunopositivity towards the cytoplasm. Our study demonstrates that diabetes mellitus (DM) increases the mRNA expression, protein level, Ser23 phosphorylation and enzyme activity of renal NKA, which is further elevated by ANGII. Despite an increase in total NKA quantity in diabetic nephropathy, the redistribution to the cystosol suggests the Na + pump is no longer functional. ANGII also caused translocation from the basolateral membrane, thus in diabetic states where ANGII level is acutely elevated, the loss of NKA will be exacerbated. This provides another mechanism by which ANGII blockade is likely to be protective.
Az ACE es a glutation peroxidaz gen polimorfizmusa osszefuggest mutat a metabolikus szindroma sul... more Az ACE es a glutation peroxidaz gen polimorfizmusa osszefuggest mutat a metabolikus szindroma sulyossagaval, es az oxidativ stressz mertekevel. A karbonil stressz egyik forrasakent ismert dohanyfust a metabolikus szindroma pathogeneziseben fontos szerepet jatszo endothel funkciot karositja. Az agyat ert karbonil stressz metabolikus szindromara jellegzetes klinikai kep kialakulasahoz vezet. A metabolikus szindromas allatok vesejeben a karbonil stressz vegtermekei es a renin kolokalizaciot mutat. Izolalt vorosvertestekben a karbonil stressz fokozott oxidativ stresszt okoz. A karbonil-stresszel jaro diabeteszes glukozuria a vese tubularis sejtjeiben hidroxil szabadgyok- termeleshez vezet. Az oxidativ stressz fontos szerepet jatszik a diabeteszes cataracta, a diabeteszes mikroalbuminuria kialakulasaban es merteke osszefugg a diabeteszes erkarosodas mertekevel. A karbonil es oxidativ stressz hatasara kepződő glikacios vegtermekek szintje a halalozas fuggetlen prediktora. Diabeteszes bete...