R. Kinscherf | Philipps University Marburg (original) (raw)
Papers by R. Kinscherf
The FASEB Journal, 2001
Sphingomyelinase (SMase) stimulation and subsequent ceramide generation are suggested to be invol... more Sphingomyelinase (SMase) stimulation and subsequent ceramide generation are suggested to be involved in signal transduction of stress-induced apoptosis. We now show that apoptosis of human macrophages (MPhi) and fibroblasts initiated by oxidized low density lipoproteins (minimally modified LDL, mmLDL) is associated with an increase in acid SMase (aSMase, E.C. 3.1.4.12) expression and ceramide concentration. Application of a novel, potent, and specific inhibitor of aSMase expression (NB6) diminished the effects of mmLDL and C6-ceramide treatment by inhibiting transcription via Sp1 and AP-2. Moreover, apoptosis was abolished after mmLDL and C6-ceramide treatment of hereditary aSMase-deficient fibroblasts (from Niemann-Pick patients). We suggest that in mmLDL-initiated apoptosis 1) enhanced ceramide generation via aSMase appears to be required as well as 2) a positive feedback control of aSMase expression by the increase in intracellular ceramide concentration.
Methods in …, 1995
[231 THIOLS AND THE IMMUNE SYSTEM 255 [23l Thiols and the Immune System: Effect of N-Acetylcystei... more [231 THIOLS AND THE IMMUNE SYSTEM 255 [23l Thiols and the Immune System: Effect of N-Acetylcysteine on T Cell System in Human Subjects By WULF DROGE, RALF KINSCHERF, SABINE MIHM, DAGMAR GALTER, STEFFEN ROTH, HELMUT GMONDER, ...
Atherosclerosis Supplements, 2010
Journal of leukocyte biology, 1997
We investigated the effect of alterations of blood cholesterol levels on macrophages (mphi) in th... more We investigated the effect of alterations of blood cholesterol levels on macrophages (mphi) in the myocardium of New Zealand White (NZW) rabbits. Three groups of NZW rabbits were used: controls, rabbits fed a 0.5% cholesterol-enriched diet (CH-D) for 96 days, and rabbits fed a 0.5% CH-D for 96 days followed by normal chow for 4 months. Immunohistochemical analysis by mAbs directed against mphi (RAM-11) and Mn superoxide dismutase (MnSOD) were quantified by computer-assisted morphometry. Using cultured human and rabbit mphi, a cross-reaction of the human MnSOD mAbs was found as well as the predominant localization of MnSOD-immunoreactivity (IR) in mitochondria. In group 1, only a very few RAM-11-immunoreactive (ir) mphi occurred in the interstitial space of the myocardium. In group II blood cholesterol levels significantly increased in parallel with the numbers of mphi, which often contained lipid droplets (foam cells). Although blood cholesterol concentrations regressed about 10-fol...
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 1997
Patients with skeletal muscle catabolism (cachexia) fail to conserve the skeletal muscle protein ... more Patients with skeletal muscle catabolism (cachexia) fail to conserve the skeletal muscle protein and release large amounts of nitrogen as urea. Previous studies suggest that the threshold for the conversion of amino acids into other forms of chemical energy and the concomitant production of urea are regulated by the plasma cystine level and hepatic cysteine catabolism. Studies of plasma amino acid exchange rates in the lower extremities now show that healthy young subjects regulate their plasma cystine level in a process that may be described as controlled constructive catabolism. The term controlled describes the fact that the release of cystine and other amino acids from the peripheral tissue is negatively correlated with (certain) plasma amino acid levels. The term constructive describes the fact that the release of cystine is correlated with an increase of the plasma cystine level. The regulation of the plasma cystine level is disturbed in conditions with progressive skeletal mu...
Neuroscience Letters, 1997
Copper/zinc-superoxide dismutase (Cu/Zn-SOD) belongs to a class of enzymes, identified as essenti... more Copper/zinc-superoxide dismutase (Cu/Zn-SOD) belongs to a class of enzymes, identified as essential and highly effective endogenous scavengers of cytotoxic oxygen radicals. These radicals contribute to postlesional neurotoxicity. In order to determine the superoxidescavenging potential of regions affected by unilateral cortical photothrombosis, we studied the changes in the distribution of Cu/Zn-SOD and the appearance of activated microglia by immunohistochemistry and isolectin B 4 binding. Four hours postlesion, Cu/Zn-SOD increased significantly within a homotopic area of the contralateral hemisphere and in ipsilateral thalamic nuclei, whereas isolectin B 4-positive microglia were upregulated at days 5 and 7 postlesion within the same regions. The contralateral increase in the amount of the superoxidescavenging Cu/Zn-SOD indicates that this enzyme is induced by a retrograde reaction carried through callosal connections.
Medicine & Science in Sports & Exercise, 1999
European Journal of Nuclear Medicine, 2001
The relation between tumour metabolism and induction of apoptosis by gene therapy was investigate... more The relation between tumour metabolism and induction of apoptosis by gene therapy was investigated in a rat Morris hepatoma (MH3924A) model expressing the HSV thymidine kinase (HSVtk) gene. In vivo the amount of glucose transporter (GLUT1 and GLUT3 isoforms) expressing cells was determined in tumours of untreated and treated animals using immunohistochemistry. In vitro uptake studies with 2-fluoro-2-deoxy-D-glucose (FDG), 3-O-methylglucose and thymidine (TdR) and a TUNEL (TdT-mediated dUTP nick end labelling) assay for the assessment of apoptosis were done immediately and 24 h after treatment of the recombinant cells with different doses of ganciclovir (GCV). Immunohistochemistry revealed a significant increase in GLUT1 in treated tumours which showed enhanced transport activity for FDG. In vitro the FDG and 3-O-methylglucose uptake increased to 186% when compared with that of the non-treated cells immediately after incubation with GCV. However, 24 h later the FDG uptake had declined to its normal level, whereas the accumulation of 3-Omethylglucose remained elevated. The uptake of TdR, which was determined simultaneously, decreased in the acid-insoluble fraction of the cells to 27% and 11%, respectively, immediately and 24 h after therapy, while in the acid-soluble fraction it increased to 229% and to 167%, respectively. Employing the TUNEL technique, 25% of cells were found to be apoptotic 24 h after the termination of GCV treatment. Inhibition of glucose transport by cytochalasin B or competition with deoxyglucose resulted in a 78% (cytochalasin B) and 88% (deoxyglucose) decrease in FDG uptake in the recombinant hepatoma cells and in an increase in the apoptotic cell fraction. It is concluded that inhibition of enhanced glucose transport in GCV-treated cells increased apoptosis. Therefore, enhanced glucose transport seems to represent a stress reaction of tumour cells dedicated for the prevention of cell death.
Arzneimittelforschung, 2011
An aqueous extract of propolis and the phenolic component of propolis, propol, were assayed for a... more An aqueous extract of propolis and the phenolic component of propolis, propol, were assayed for antioxidative and antiapoptotic properties. Both additions inhibited Cu(2+)-initiated low density lipoprotein (LDL) oxidation as characterized by a reduction of the lag time, reduced the increase of relative electrophoretic mobility during oxidation and markedly diminished apoptosis of human macrophages exposed to minimally modified (mmLDL). Moreover, aqueous propolis extract and propol blocked the mmLDL-induced decrease of glutathione (GSH) and the activation of the transcription factor NF-kappa B in these cells. The potent phenolic antioxidant propol thus expands the capability of cells to neutralize oxidative stress and to prevent apoptosis and is therefore suggested to significantly contribute to the antiinflammatory and antioxidative effects of propolis.
Cell and Tissue Research, 1997
Physiological data indicate a residual vascularisation within ischemic myocardial regions where n... more Physiological data indicate a residual vascularisation within ischemic myocardial regions where necrosis of most cells have been reported to occur after myocardial infarction. We therefore studied, by means of immunohistochemistry, computer-assisted morphometry, and electron microscopy, the terminal vascularisation in correlation to cardiomyocytes in ten canine hearts 1 and 3 weeks after occlusion of the left anterior descending (LAD) coronary artery. In comparison to non-infarcted myocardium we found the following alterations in infarcted myocardium: (1) the area density of cardiomyocytes decreased from 98% (control) to 7.9% (1 week after occlusion) and to 2.7% (3 weeks after occlusion); (2) the number of capillaries was diminished to 11.6% and to 2.6%; respectively; (3) smooth muscle alpha-actin was induced in endothelial (EC) cells of the microvessels; and (4) terminal resistance vessels increased 11-fold and 20-fold in number, respectively. Our findings confirm the necrosis of the vast majority of cardiomyocytes and capillaries within the first 3 weeks after myocardial infarction. Besides a small number of capillaries, many terminal resistance vessels, however, seem to persist in the scarring infarcted tissue. The occurrence of these microvessels is supposed to be important for the granulation tissue as well as for the control and regulation of a residual blood supply during scar formation.
Zeitschrift für Phytotherapie, 2016
Atherosclerosis Supplements, 2007
Ultraschall in der Medizin - European Journal of Ultrasound, 2007
Zeitschrift für Phytotherapie, 2008
Zeitschrift für Phytotherapie, 2009
Zeitschrift für Phytotherapie, 2008
ABSTRACT STW 5 (Iberogast®) is a phytomedicinal combination of nine herbal extracts indicated for... more ABSTRACT STW 5 (Iberogast®) is a phytomedicinal combination of nine herbal extracts indicated for functional gastro-intestinal diseases. As subchronic inflammation is one of the pathophysiological causes of these diseases, the aim of this study was to determine anti-inflammatory effects of STW 5 and its components in comparison to well characterized NSAIDs such as acetylsalicylic acid and diclofenac. As a model HT-29 colon cancer cells were chosen, as it is known, that NSAIDs cause, via their inhibitory effect on COXs, an inhibition of their proliferation, as indicated by the release of lactate dehydrogenase (LDH) and by measuring Sulforhodamine B (SRB). Apoptosis was identified by YO-PRO-1 staining in combination with Hoechst 33342 dye. Intracellular translocation of the NFκ-B p65 subunit was analyzed in THP-1 cells line after differentiation with PMA, pre-treatment with the compounds, and afterward activation with LPS. The treatment of HT-29 colon carcinoma cells with diclofenac and Aspirin® was found to inhibit proliferation significantly. The same was the case with STW 5 and its components. Especially STW 6 (Iberis amara totalis), but also STW 5-K II (peppermint leaves), STW 5-K VII (milk thistle fruit) and STW 5-K VIII (lemon balm leaves) inhibited proliferation of the cancer cells significantly. Moreover, STW 5 treatment of the differentiated THP-1 cells inhibited the induction of the NFκ-B p65 translocation into the cell nucleus after activation with LPS. In conclusion, our present data suggest that STW 5 (Iberogast®) and its components STW 6, STW 5-K II, STW 5-K VII and STW 5-K VIII may have significant anti-inflammatory properties, relevant in the treatment of functional gastrointestinal diseases, and in addition also anti-cancer effects. Z Phytother 2008; 29 - P03; DOI: 10.1055/s-2008-1047850
The FASEB Journal, 2001
Sphingomyelinase (SMase) stimulation and subsequent ceramide generation are suggested to be invol... more Sphingomyelinase (SMase) stimulation and subsequent ceramide generation are suggested to be involved in signal transduction of stress-induced apoptosis. We now show that apoptosis of human macrophages (MPhi) and fibroblasts initiated by oxidized low density lipoproteins (minimally modified LDL, mmLDL) is associated with an increase in acid SMase (aSMase, E.C. 3.1.4.12) expression and ceramide concentration. Application of a novel, potent, and specific inhibitor of aSMase expression (NB6) diminished the effects of mmLDL and C6-ceramide treatment by inhibiting transcription via Sp1 and AP-2. Moreover, apoptosis was abolished after mmLDL and C6-ceramide treatment of hereditary aSMase-deficient fibroblasts (from Niemann-Pick patients). We suggest that in mmLDL-initiated apoptosis 1) enhanced ceramide generation via aSMase appears to be required as well as 2) a positive feedback control of aSMase expression by the increase in intracellular ceramide concentration.
Methods in …, 1995
[231 THIOLS AND THE IMMUNE SYSTEM 255 [23l Thiols and the Immune System: Effect of N-Acetylcystei... more [231 THIOLS AND THE IMMUNE SYSTEM 255 [23l Thiols and the Immune System: Effect of N-Acetylcysteine on T Cell System in Human Subjects By WULF DROGE, RALF KINSCHERF, SABINE MIHM, DAGMAR GALTER, STEFFEN ROTH, HELMUT GMONDER, ...
Atherosclerosis Supplements, 2010
Journal of leukocyte biology, 1997
We investigated the effect of alterations of blood cholesterol levels on macrophages (mphi) in th... more We investigated the effect of alterations of blood cholesterol levels on macrophages (mphi) in the myocardium of New Zealand White (NZW) rabbits. Three groups of NZW rabbits were used: controls, rabbits fed a 0.5% cholesterol-enriched diet (CH-D) for 96 days, and rabbits fed a 0.5% CH-D for 96 days followed by normal chow for 4 months. Immunohistochemical analysis by mAbs directed against mphi (RAM-11) and Mn superoxide dismutase (MnSOD) were quantified by computer-assisted morphometry. Using cultured human and rabbit mphi, a cross-reaction of the human MnSOD mAbs was found as well as the predominant localization of MnSOD-immunoreactivity (IR) in mitochondria. In group 1, only a very few RAM-11-immunoreactive (ir) mphi occurred in the interstitial space of the myocardium. In group II blood cholesterol levels significantly increased in parallel with the numbers of mphi, which often contained lipid droplets (foam cells). Although blood cholesterol concentrations regressed about 10-fol...
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 1997
Patients with skeletal muscle catabolism (cachexia) fail to conserve the skeletal muscle protein ... more Patients with skeletal muscle catabolism (cachexia) fail to conserve the skeletal muscle protein and release large amounts of nitrogen as urea. Previous studies suggest that the threshold for the conversion of amino acids into other forms of chemical energy and the concomitant production of urea are regulated by the plasma cystine level and hepatic cysteine catabolism. Studies of plasma amino acid exchange rates in the lower extremities now show that healthy young subjects regulate their plasma cystine level in a process that may be described as controlled constructive catabolism. The term controlled describes the fact that the release of cystine and other amino acids from the peripheral tissue is negatively correlated with (certain) plasma amino acid levels. The term constructive describes the fact that the release of cystine is correlated with an increase of the plasma cystine level. The regulation of the plasma cystine level is disturbed in conditions with progressive skeletal mu...
Neuroscience Letters, 1997
Copper/zinc-superoxide dismutase (Cu/Zn-SOD) belongs to a class of enzymes, identified as essenti... more Copper/zinc-superoxide dismutase (Cu/Zn-SOD) belongs to a class of enzymes, identified as essential and highly effective endogenous scavengers of cytotoxic oxygen radicals. These radicals contribute to postlesional neurotoxicity. In order to determine the superoxidescavenging potential of regions affected by unilateral cortical photothrombosis, we studied the changes in the distribution of Cu/Zn-SOD and the appearance of activated microglia by immunohistochemistry and isolectin B 4 binding. Four hours postlesion, Cu/Zn-SOD increased significantly within a homotopic area of the contralateral hemisphere and in ipsilateral thalamic nuclei, whereas isolectin B 4-positive microglia were upregulated at days 5 and 7 postlesion within the same regions. The contralateral increase in the amount of the superoxidescavenging Cu/Zn-SOD indicates that this enzyme is induced by a retrograde reaction carried through callosal connections.
Medicine & Science in Sports & Exercise, 1999
European Journal of Nuclear Medicine, 2001
The relation between tumour metabolism and induction of apoptosis by gene therapy was investigate... more The relation between tumour metabolism and induction of apoptosis by gene therapy was investigated in a rat Morris hepatoma (MH3924A) model expressing the HSV thymidine kinase (HSVtk) gene. In vivo the amount of glucose transporter (GLUT1 and GLUT3 isoforms) expressing cells was determined in tumours of untreated and treated animals using immunohistochemistry. In vitro uptake studies with 2-fluoro-2-deoxy-D-glucose (FDG), 3-O-methylglucose and thymidine (TdR) and a TUNEL (TdT-mediated dUTP nick end labelling) assay for the assessment of apoptosis were done immediately and 24 h after treatment of the recombinant cells with different doses of ganciclovir (GCV). Immunohistochemistry revealed a significant increase in GLUT1 in treated tumours which showed enhanced transport activity for FDG. In vitro the FDG and 3-O-methylglucose uptake increased to 186% when compared with that of the non-treated cells immediately after incubation with GCV. However, 24 h later the FDG uptake had declined to its normal level, whereas the accumulation of 3-Omethylglucose remained elevated. The uptake of TdR, which was determined simultaneously, decreased in the acid-insoluble fraction of the cells to 27% and 11%, respectively, immediately and 24 h after therapy, while in the acid-soluble fraction it increased to 229% and to 167%, respectively. Employing the TUNEL technique, 25% of cells were found to be apoptotic 24 h after the termination of GCV treatment. Inhibition of glucose transport by cytochalasin B or competition with deoxyglucose resulted in a 78% (cytochalasin B) and 88% (deoxyglucose) decrease in FDG uptake in the recombinant hepatoma cells and in an increase in the apoptotic cell fraction. It is concluded that inhibition of enhanced glucose transport in GCV-treated cells increased apoptosis. Therefore, enhanced glucose transport seems to represent a stress reaction of tumour cells dedicated for the prevention of cell death.
Arzneimittelforschung, 2011
An aqueous extract of propolis and the phenolic component of propolis, propol, were assayed for a... more An aqueous extract of propolis and the phenolic component of propolis, propol, were assayed for antioxidative and antiapoptotic properties. Both additions inhibited Cu(2+)-initiated low density lipoprotein (LDL) oxidation as characterized by a reduction of the lag time, reduced the increase of relative electrophoretic mobility during oxidation and markedly diminished apoptosis of human macrophages exposed to minimally modified (mmLDL). Moreover, aqueous propolis extract and propol blocked the mmLDL-induced decrease of glutathione (GSH) and the activation of the transcription factor NF-kappa B in these cells. The potent phenolic antioxidant propol thus expands the capability of cells to neutralize oxidative stress and to prevent apoptosis and is therefore suggested to significantly contribute to the antiinflammatory and antioxidative effects of propolis.
Cell and Tissue Research, 1997
Physiological data indicate a residual vascularisation within ischemic myocardial regions where n... more Physiological data indicate a residual vascularisation within ischemic myocardial regions where necrosis of most cells have been reported to occur after myocardial infarction. We therefore studied, by means of immunohistochemistry, computer-assisted morphometry, and electron microscopy, the terminal vascularisation in correlation to cardiomyocytes in ten canine hearts 1 and 3 weeks after occlusion of the left anterior descending (LAD) coronary artery. In comparison to non-infarcted myocardium we found the following alterations in infarcted myocardium: (1) the area density of cardiomyocytes decreased from 98% (control) to 7.9% (1 week after occlusion) and to 2.7% (3 weeks after occlusion); (2) the number of capillaries was diminished to 11.6% and to 2.6%; respectively; (3) smooth muscle alpha-actin was induced in endothelial (EC) cells of the microvessels; and (4) terminal resistance vessels increased 11-fold and 20-fold in number, respectively. Our findings confirm the necrosis of the vast majority of cardiomyocytes and capillaries within the first 3 weeks after myocardial infarction. Besides a small number of capillaries, many terminal resistance vessels, however, seem to persist in the scarring infarcted tissue. The occurrence of these microvessels is supposed to be important for the granulation tissue as well as for the control and regulation of a residual blood supply during scar formation.
Zeitschrift für Phytotherapie, 2016
Atherosclerosis Supplements, 2007
Ultraschall in der Medizin - European Journal of Ultrasound, 2007
Zeitschrift für Phytotherapie, 2008
Zeitschrift für Phytotherapie, 2009
Zeitschrift für Phytotherapie, 2008
ABSTRACT STW 5 (Iberogast®) is a phytomedicinal combination of nine herbal extracts indicated for... more ABSTRACT STW 5 (Iberogast®) is a phytomedicinal combination of nine herbal extracts indicated for functional gastro-intestinal diseases. As subchronic inflammation is one of the pathophysiological causes of these diseases, the aim of this study was to determine anti-inflammatory effects of STW 5 and its components in comparison to well characterized NSAIDs such as acetylsalicylic acid and diclofenac. As a model HT-29 colon cancer cells were chosen, as it is known, that NSAIDs cause, via their inhibitory effect on COXs, an inhibition of their proliferation, as indicated by the release of lactate dehydrogenase (LDH) and by measuring Sulforhodamine B (SRB). Apoptosis was identified by YO-PRO-1 staining in combination with Hoechst 33342 dye. Intracellular translocation of the NFκ-B p65 subunit was analyzed in THP-1 cells line after differentiation with PMA, pre-treatment with the compounds, and afterward activation with LPS. The treatment of HT-29 colon carcinoma cells with diclofenac and Aspirin® was found to inhibit proliferation significantly. The same was the case with STW 5 and its components. Especially STW 6 (Iberis amara totalis), but also STW 5-K II (peppermint leaves), STW 5-K VII (milk thistle fruit) and STW 5-K VIII (lemon balm leaves) inhibited proliferation of the cancer cells significantly. Moreover, STW 5 treatment of the differentiated THP-1 cells inhibited the induction of the NFκ-B p65 translocation into the cell nucleus after activation with LPS. In conclusion, our present data suggest that STW 5 (Iberogast®) and its components STW 6, STW 5-K II, STW 5-K VII and STW 5-K VIII may have significant anti-inflammatory properties, relevant in the treatment of functional gastrointestinal diseases, and in addition also anti-cancer effects. Z Phytother 2008; 29 - P03; DOI: 10.1055/s-2008-1047850