Vijayan Elimban - Academia.edu (original) (raw)

Papers by Vijayan Elimban

Canadian journal of physiology and pharmacology, Jan 30, 2018

The effects of CO2 water-bath therapy in the hind limb of diabetic animals with or without periph... more The effects of CO2 water-bath therapy in the hind limb of diabetic animals with or without peripheral ischemia were examined. Diabetes was induced in rats by streptozotocin (65 mg/kg) and the animals were divided into three groups. After 4 weeks, peripheral ischemia was induced by ligation of the femoral artery for 2 weeks in two groups (Diabetic Ischemic) of diabetic rats, whereas the femoral artery was not occluded in the third group (Diabetic). All these animals were subjected to water-bath therapy (with or without CO2 mixing; 20 min per day for 5 days per week) for a period of 4 weeks. Both peak and mean flows, unlike minimal flow, in diabetic ischemic limbs were increased by about 2 fold by CO2 bath treatment. Morphological examination of hind limb tissue sections revealed about 2 fold increase in the small artery count in diabetic ischemic animals upon CO2 bath treatment. These results indicate that CO2 water-bath therapy augments the blood flow and development of angiogenesis...

Canadian Journal of Physiology and Pharmacology

In this study, we investigated the effects of CO2 water-bath therapy on blood flow and angiogenes... more In this study, we investigated the effects of CO2 water-bath therapy on blood flow and angiogenesis in the ischemic hind limb, as well as some plasma angiogenic factors in peripheral ischemic model. The hind limb ischemia was induced by occluding the femoral artery for 2 weeks in rats and treated with or without CO2 water-bath therapy at 37 °C for 4 weeks (20 min treatment every day for 5 days per week). The peak blood flow and minimal and mean blood flow in the ischemic skeletal muscle were markedly increased by the CO2 water-bath therapy. This increase in blood flow was associated with development of angiogenesis in the muscle, as well as reduction in the ischemia-induced increase in plasma malondialdehyde levels. Although plasma vascular endothelial growth factor and nitric oxide levels were increased in animals with peripheral ischemia, the changes in these biomarkers were not affected by CO2 water-bath therapy. These results suggest that augmentation of blood flow in the ischem...

Molecular and Cellular Biochemistry

Although CO is produced during the oxidation of different substrates in all types of cells, the r... more Although CO is produced during the oxidation of different substrates in all types of cells, the role of this gas in the regulation of cellular function is not clearly understood. Since changes in several signal transduction as well as apoptotic, anti-apoptotic, and other proteins are known to modify cellular function, we investigated if some of these proteins are altered upon incubating the rat hind leg skeletal muscle in a medium enriched with CO (1000-1200 ppm) for 30 min. CO was observed to depress phosphorylated levels of ERK1 (P44) and ERK2 (P42) without affecting the unphosphorylated content of these MAPK proteins. On the other hand, no change in p38 MAPK protein was found but the content of its degradation product 30 kDa proteins (both phosphorylated and unphosphorylated) was decreased. No alterations in the content of other signaling proteins (PKA and Akt), inflammatory molecule (TNF-α), and vascular endothelial growth factor (VEGF) were seen upon exposure of the muscle to CO. The content for apoptotic and anti-apoptotic proteins (Bad and Bcl2), except for a decrease in caspase 3, were also not affected by CO. These results indicate that CO may serve as a gasotransmitter to regulate cellular function by depressing MAPK and caspase 3 activities.

福山大学薬学部研究年報 Annual Report of the Faculty of Pharmacy Pharmaceutical Sciences Fukuyama University, 1986

Research Communications in Chemical Pathology and Pharmacology, Sep 1, 1984

Sarcolemmal Ca2+/Mg2+ ATPase was inhibited only about 30% by myosin antiserum that decreased myof... more Sarcolemmal Ca2+/Mg2+ ATPase was inhibited only about 30% by myosin antiserum that decreased myofibrillar ATPase activity by about 80%. There was a remarkable difference in the effect of myosin antiserum on sarcolemmal Ca2+/Mg2+ ATPase and myofibrillar ATPase with regard to its pre-incubation time with these organelles. Tryptic digestion of the sarcolemmal membrane did not show any change in its inhibitory effect of the myosin antiserum on Ca2+ ATPase. The data distinguish the Ca2+/Mg2+ ATPase from myosin ATPase and suggest that it is an enzyme of the sarcolemmal origin.

Journal of cellular and molecular medicine, 2015

The voltage-operated Ca(2+) channels (VOCC), which allow Ca(2+) influx from the extracellular spa... more The voltage-operated Ca(2+) channels (VOCC), which allow Ca(2+) influx from the extracellular space, are inhibited by anti-hypertensive agents such as verapamil and nifedipine. The Ca(2+) entering from outside into the cell triggers Ca(2+) release from the sarcoplasmic reticulum (SR) stores. To refill the depleted Ca(2+) stores in the SR, another type of Ca(2+) channels in the cell membrane, known as store-operated Ca(2+) channels (SOCC), are activated. These SOCCs are verapamil and nifedipine resistant, but are SKF 96465 (SK) and gadolinium (Gd(3+) ) sensitive. Both SK and Gd(3+) have been shown to reduce [Ca(2+) ]i in the smooth muscle, but their effects on blood pressure have not been reported. Our results demonstrated that both SK and Gd(3+) produced a dose-dependent reduction in blood pressure in rat. The combination of SK and verapamil produced an additive action in lowering the blood pressure. Furthermore, SK, but not Gd(3+) suppressed proliferation of vascular smooth muscle ...

Molecular and Cellular Biochemistry, 1994

To define metabolic influences on cardiac myosin expression and sarcoplasmic reticulum (SR) Ca(2+... more To define metabolic influences on cardiac myosin expression and sarcoplasmic reticulum (SR) Ca(2+)-stimulated ATPase streptozotocin-diabetic rats were treated for 9-10 wk with etomoxir, an inhibitor of carnitine palmitoyl transferase I (CPT-1) and fatty acid synthesis, or an antilipolytic drug, acipimox. Etomoxir reduced myosin V3 of diabetic rats but did not normalize it. However, the high serum triglyceride, free-fatty acid and cholesterol concentrations in diabetic animals were greatly reduced. After bypassing the CPT-1 inhibition with a medium-chain fatty acid (miglyol) diet, the V3 contents and serum lipids were still reduced in the etomoxir-treated diabetic rats; V3 was also reduced in diabetic rats fed miglyol or treated with acipimox. Since low serum insulin or triiodothyronine concentrations in diabetic rats were not improved by these interventions but changes in V3 were correlated with those in triglyceride, free-fatty acid and cholesterol concentrations, it is likely that myosin may be influenced by some metabolic factors. To assess the role of adrenergic influences, diabetic rats (7-8 wk) were treated with an antisympathotonic drug, moxonidine, a beta-adrenoceptor blocking drug, propranolol, and a bradycardic drug, tedisamil. Myosin V3 was not reduced significantly in moxonidine-treated or propranolol-treated rats in comparison to untreated diabetic rats. Serum thyroid hormones and insulin were not altered, whereas triglycerides were reduced but not significantly by these antiadrenergic agents. Lowering serum lipids in diabetic rats by treatment with etomoxir, miglyol and acipimox increased the depressed SR Ca(2+)-stimulated ATPase activity. On the other hand, in diabetic rats treated with moxonidine, propranolol or tedisamil, the ATPase activity was not increased significantly. These results suggest that normalization of blood lipids is important for improving subcellular organelle function in diabetic hearts with impaired glucose utilization.

Journal of Molecular and Cellular Cardiology, Nov 30, 1998

In order to examine the status of G-proteins in congestive heart failure due to myocardial infarc... more In order to examine the status of G-proteins in congestive heart failure due to myocardial infarction, the left coronary artery in rats was ligated and animals assessed after 4, 8 and 16 weeks. Sham-operated control and experimental animals were used for the preparation of membranes from the viable (uninfarcted) left and right ventricles. Adenylyl cyclase activities in the presence of pertussis toxin and cholera toxin were increased and decreased in left ventricles from all groups, respectively. On the other hand, adenylyl cyclase activities in 8 and 16-week experimental right ventricles were unaltered in the presence of pertussis toxin and increased in the presence of cholera toxin. Depression of adenylyl cyclase activities in left ventricles from all groups as well as in the right ventricle at 4 weeks were not evident when enzyme activity was determined in the pertussis toxin-treated membranes in the absence or presence of Gpp(NH)p. Cholera toxincatalyzed ADP ribosylation was decreased in left ventricles from all infarcted groups and increased in the right ventricles at 8 and 16 weeks whereas the pertussis toxin-catalyzed ADP ribosylation was increased in all experimental tissues except in the right ventricles at 8 and 16 weeks. G s-protein content was decreased in the left ventricle at 16 weeks and increased in the right ventricles at 8 and 16 weeks of myocardial infarction. On the other hand, G i-protein content was increased in left ventricles from all infarcted groups and the 4-week right ventricle but was unaltered in 8 and 16-week right ventricles. An increase in mRNA abundance for G i-protein was seen in both left and right ventricles following myocardial infarction. A significant increase in mRNA level for G s-protein was observed in all left ventricles and 8-week right ventricle following the coronary occlusion. These results suggest that changes in G sand G i-proteins in the failing heart due to myocardial infarction are chamber-specific and are dependent upon the stage of congestive heart failure.

Experimental and Clinical Cardiology, Feb 1, 2003

By virtue of its ability to enhance glucose uptake and oxidation in the cell, vanadate is known t... more By virtue of its ability to enhance glucose uptake and oxidation in the cell, vanadate is known to exert an insulin-like action in the body. Because defects in substrate use and energy generation are considered to play an important role in cardiac contractile dysfunction as a consequence of ischemia-reperfusion (I/R), this study was carried out to examine the effects of vanadate on I/R-induced changes in cardiac performance and sarcoplasmic reticulum (SR) function. For this purpose, isolated rat hearts were subjected to global ischemia for 30 min and then reperfused for 30 min with normal perfusion medium in the absence or presence of different concentrations of vanadate. The left ventricular developed pressure, rate of contraction and rate of relaxation were depressed, whereas the left ventricular end-diastolic pressure was increased in the ischemic-reperfused heart. However, these abnormalities were attenuated on treatment of the heart with 1 μM and 4 μM of vanadate. The SR preparation isolated from the ischemic-reperfused hearts showed a marked depression in calcium uptake and ryanodine binding (calcium release channel) activities; these defects were attenuated by the addition of vanadate to the perfusion medium. The results demonstrate beneficial effects of vanadate on cardiac dysfunction and changes in SR calcium transport due to I/R injury.

Journal of Pharmacology and Experimental Therapeutics, Apr 1, 2000

Although β-adrenoceptor (β-AR) blockers are used for the treatment of ischemic heart disease, the... more Although β-adrenoceptor (β-AR) blockers are used for the treatment of ischemic heart disease, the mechanisms of their beneficial actions have not been fully elucidated. In view of the role of sarcoplasmic reticular (SR) abnormalities in cardiac dysfunction due to ...

Regulation of Ca2+-ATPases,V-ATPases and F-ATPases, 2015

J Appl Physiol, 2006

To examine whether cardiac hypertrophy is associated with changes in β-adrenoceptor signal transd... more To examine whether cardiac hypertrophy is associated with changes in β-adrenoceptor signal transduction mechanisms, pressure overload (PO) was induced by occlusion of the abdominal aorta and volume overload (VO) by creation of an aortocaval shunt for 4 and 24 wk in rats. After hemodynamic assessment of the animals, the left ventricular (LV) particulate fraction was isolated for measurement of β1-adrenoceptors and adenylyl cyclase activity, and cardiomyocytes were isolated for monitoring of the intracellular Ca2+ concentration. Although PO and VO produced cardiac hypertrophy and increased LV end-diastolic pressure at 4 wk, cardiac function was increased in animals subjected to PO but remained unaltered in animals subjected to VO. Cardiac hypertrophy and increased LV end-diastolic pressure were associated with depressed cardiac function at 24 wk of PO or VO, but clinical signs of congestive heart failure were evident only in animals subjected to VO. Isoproterenol-induced increases in cardiac function, activation of adenylyl cyclase activity, and increase in intracellular Ca2+ concentration, as well as β1-adrenoceptor density, were unaltered by PO at 4 wk, augmented by VO at 4 wk, and attenuated by PO and VO at 24 wk. These results suggest that alterations in β1-adrenoceptor signal transduction are dependent on the type and stage of cardiac hypertrophy.

Experimental and Clinical Cardiology, Feb 1, 2003

BACKGROUND:Mitogen-activated protein kinases (MAPKs) are involved in the regulation of various ce... more BACKGROUND:Mitogen-activated protein kinases (MAPKs) are involved in the regulation of various cellular responses including cell proliferation, differentiation and survival. Although MAPKs are activated by MAPK kinase and inactivated by phosphatases, different types of MAPKs, including extracellular signal-regulated kinases (ERK1 and 2), c-jun N-terminal protein kinases (JNK) and p38 kinases are known to participate in different signalling pathways. This article will review some salient features of the regulation and function of different forms of MAPKs in the heart. Furthermore, the status of cardiac MAPKs under different pathophysiological conditions will be described.OBSERVATIONS:A wide variety of external stimuli are known to activate MAPKs, which are then translocated from the cytoplasm to the nucleus and regulate cardiac gene expression by phosphorylating various transcriptional factors. By virtue of the involvement of ERK1/2 in hypertrophic response and of the stress-activated JNKs and p38 kinases in the process of apoptosis, MAPKs are considered to be intimately involved in cardiac remodelling. Both growth factors and phorbol esters have been shown to strongly activate ERK1/2, whereas the activation of JNKs and p38 kinases by these agents is weak. Although ischemia-reperfusion activates all types of MAPKs, JNKs and p38 kinases are mainly proapoptotic, whereas ERK1/2 are antiapoptotic.CONCLUSIONS:The activation of ERK1/2 is involved in signal transduction pathways associated with cardiac hypertrophy; however, the exact status of MAPKs in heart failure remains to be clearly defined. While both JNKs and p38 kinases appear to participate in the genesis of ischemia-reperfusion injury, ERK1/2 are considered to be cytoprotective.

Journal of Cardiovascular Pharmacology and Therapeutics, 2010

Cardiac Energy Metabolism in Health and Disease, 2014

Developments in Cardiovascular Medicine, 1996

Role of Proteases in Cellular Dysfunction, 2013

Proteases in Health and Disease, 2013

Canadian journal of physiology and pharmacology, Jan 30, 2018

The effects of CO2 water-bath therapy in the hind limb of diabetic animals with or without periph... more The effects of CO2 water-bath therapy in the hind limb of diabetic animals with or without peripheral ischemia were examined. Diabetes was induced in rats by streptozotocin (65 mg/kg) and the animals were divided into three groups. After 4 weeks, peripheral ischemia was induced by ligation of the femoral artery for 2 weeks in two groups (Diabetic Ischemic) of diabetic rats, whereas the femoral artery was not occluded in the third group (Diabetic). All these animals were subjected to water-bath therapy (with or without CO2 mixing; 20 min per day for 5 days per week) for a period of 4 weeks. Both peak and mean flows, unlike minimal flow, in diabetic ischemic limbs were increased by about 2 fold by CO2 bath treatment. Morphological examination of hind limb tissue sections revealed about 2 fold increase in the small artery count in diabetic ischemic animals upon CO2 bath treatment. These results indicate that CO2 water-bath therapy augments the blood flow and development of angiogenesis...

Canadian Journal of Physiology and Pharmacology

In this study, we investigated the effects of CO2 water-bath therapy on blood flow and angiogenes... more In this study, we investigated the effects of CO2 water-bath therapy on blood flow and angiogenesis in the ischemic hind limb, as well as some plasma angiogenic factors in peripheral ischemic model. The hind limb ischemia was induced by occluding the femoral artery for 2 weeks in rats and treated with or without CO2 water-bath therapy at 37 °C for 4 weeks (20 min treatment every day for 5 days per week). The peak blood flow and minimal and mean blood flow in the ischemic skeletal muscle were markedly increased by the CO2 water-bath therapy. This increase in blood flow was associated with development of angiogenesis in the muscle, as well as reduction in the ischemia-induced increase in plasma malondialdehyde levels. Although plasma vascular endothelial growth factor and nitric oxide levels were increased in animals with peripheral ischemia, the changes in these biomarkers were not affected by CO2 water-bath therapy. These results suggest that augmentation of blood flow in the ischem...

Molecular and Cellular Biochemistry

Although CO is produced during the oxidation of different substrates in all types of cells, the r... more Although CO is produced during the oxidation of different substrates in all types of cells, the role of this gas in the regulation of cellular function is not clearly understood. Since changes in several signal transduction as well as apoptotic, anti-apoptotic, and other proteins are known to modify cellular function, we investigated if some of these proteins are altered upon incubating the rat hind leg skeletal muscle in a medium enriched with CO (1000-1200 ppm) for 30 min. CO was observed to depress phosphorylated levels of ERK1 (P44) and ERK2 (P42) without affecting the unphosphorylated content of these MAPK proteins. On the other hand, no change in p38 MAPK protein was found but the content of its degradation product 30 kDa proteins (both phosphorylated and unphosphorylated) was decreased. No alterations in the content of other signaling proteins (PKA and Akt), inflammatory molecule (TNF-α), and vascular endothelial growth factor (VEGF) were seen upon exposure of the muscle to CO. The content for apoptotic and anti-apoptotic proteins (Bad and Bcl2), except for a decrease in caspase 3, were also not affected by CO. These results indicate that CO may serve as a gasotransmitter to regulate cellular function by depressing MAPK and caspase 3 activities.

福山大学薬学部研究年報 Annual Report of the Faculty of Pharmacy Pharmaceutical Sciences Fukuyama University, 1986

Research Communications in Chemical Pathology and Pharmacology, Sep 1, 1984

Sarcolemmal Ca2+/Mg2+ ATPase was inhibited only about 30% by myosin antiserum that decreased myof... more Sarcolemmal Ca2+/Mg2+ ATPase was inhibited only about 30% by myosin antiserum that decreased myofibrillar ATPase activity by about 80%. There was a remarkable difference in the effect of myosin antiserum on sarcolemmal Ca2+/Mg2+ ATPase and myofibrillar ATPase with regard to its pre-incubation time with these organelles. Tryptic digestion of the sarcolemmal membrane did not show any change in its inhibitory effect of the myosin antiserum on Ca2+ ATPase. The data distinguish the Ca2+/Mg2+ ATPase from myosin ATPase and suggest that it is an enzyme of the sarcolemmal origin.

Journal of cellular and molecular medicine, 2015

The voltage-operated Ca(2+) channels (VOCC), which allow Ca(2+) influx from the extracellular spa... more The voltage-operated Ca(2+) channels (VOCC), which allow Ca(2+) influx from the extracellular space, are inhibited by anti-hypertensive agents such as verapamil and nifedipine. The Ca(2+) entering from outside into the cell triggers Ca(2+) release from the sarcoplasmic reticulum (SR) stores. To refill the depleted Ca(2+) stores in the SR, another type of Ca(2+) channels in the cell membrane, known as store-operated Ca(2+) channels (SOCC), are activated. These SOCCs are verapamil and nifedipine resistant, but are SKF 96465 (SK) and gadolinium (Gd(3+) ) sensitive. Both SK and Gd(3+) have been shown to reduce [Ca(2+) ]i in the smooth muscle, but their effects on blood pressure have not been reported. Our results demonstrated that both SK and Gd(3+) produced a dose-dependent reduction in blood pressure in rat. The combination of SK and verapamil produced an additive action in lowering the blood pressure. Furthermore, SK, but not Gd(3+) suppressed proliferation of vascular smooth muscle ...

Molecular and Cellular Biochemistry, 1994

To define metabolic influences on cardiac myosin expression and sarcoplasmic reticulum (SR) Ca(2+... more To define metabolic influences on cardiac myosin expression and sarcoplasmic reticulum (SR) Ca(2+)-stimulated ATPase streptozotocin-diabetic rats were treated for 9-10 wk with etomoxir, an inhibitor of carnitine palmitoyl transferase I (CPT-1) and fatty acid synthesis, or an antilipolytic drug, acipimox. Etomoxir reduced myosin V3 of diabetic rats but did not normalize it. However, the high serum triglyceride, free-fatty acid and cholesterol concentrations in diabetic animals were greatly reduced. After bypassing the CPT-1 inhibition with a medium-chain fatty acid (miglyol) diet, the V3 contents and serum lipids were still reduced in the etomoxir-treated diabetic rats; V3 was also reduced in diabetic rats fed miglyol or treated with acipimox. Since low serum insulin or triiodothyronine concentrations in diabetic rats were not improved by these interventions but changes in V3 were correlated with those in triglyceride, free-fatty acid and cholesterol concentrations, it is likely that myosin may be influenced by some metabolic factors. To assess the role of adrenergic influences, diabetic rats (7-8 wk) were treated with an antisympathotonic drug, moxonidine, a beta-adrenoceptor blocking drug, propranolol, and a bradycardic drug, tedisamil. Myosin V3 was not reduced significantly in moxonidine-treated or propranolol-treated rats in comparison to untreated diabetic rats. Serum thyroid hormones and insulin were not altered, whereas triglycerides were reduced but not significantly by these antiadrenergic agents. Lowering serum lipids in diabetic rats by treatment with etomoxir, miglyol and acipimox increased the depressed SR Ca(2+)-stimulated ATPase activity. On the other hand, in diabetic rats treated with moxonidine, propranolol or tedisamil, the ATPase activity was not increased significantly. These results suggest that normalization of blood lipids is important for improving subcellular organelle function in diabetic hearts with impaired glucose utilization.

Journal of Molecular and Cellular Cardiology, Nov 30, 1998

In order to examine the status of G-proteins in congestive heart failure due to myocardial infarc... more In order to examine the status of G-proteins in congestive heart failure due to myocardial infarction, the left coronary artery in rats was ligated and animals assessed after 4, 8 and 16 weeks. Sham-operated control and experimental animals were used for the preparation of membranes from the viable (uninfarcted) left and right ventricles. Adenylyl cyclase activities in the presence of pertussis toxin and cholera toxin were increased and decreased in left ventricles from all groups, respectively. On the other hand, adenylyl cyclase activities in 8 and 16-week experimental right ventricles were unaltered in the presence of pertussis toxin and increased in the presence of cholera toxin. Depression of adenylyl cyclase activities in left ventricles from all groups as well as in the right ventricle at 4 weeks were not evident when enzyme activity was determined in the pertussis toxin-treated membranes in the absence or presence of Gpp(NH)p. Cholera toxincatalyzed ADP ribosylation was decreased in left ventricles from all infarcted groups and increased in the right ventricles at 8 and 16 weeks whereas the pertussis toxin-catalyzed ADP ribosylation was increased in all experimental tissues except in the right ventricles at 8 and 16 weeks. G s-protein content was decreased in the left ventricle at 16 weeks and increased in the right ventricles at 8 and 16 weeks of myocardial infarction. On the other hand, G i-protein content was increased in left ventricles from all infarcted groups and the 4-week right ventricle but was unaltered in 8 and 16-week right ventricles. An increase in mRNA abundance for G i-protein was seen in both left and right ventricles following myocardial infarction. A significant increase in mRNA level for G s-protein was observed in all left ventricles and 8-week right ventricle following the coronary occlusion. These results suggest that changes in G sand G i-proteins in the failing heart due to myocardial infarction are chamber-specific and are dependent upon the stage of congestive heart failure.

Experimental and Clinical Cardiology, Feb 1, 2003

By virtue of its ability to enhance glucose uptake and oxidation in the cell, vanadate is known t... more By virtue of its ability to enhance glucose uptake and oxidation in the cell, vanadate is known to exert an insulin-like action in the body. Because defects in substrate use and energy generation are considered to play an important role in cardiac contractile dysfunction as a consequence of ischemia-reperfusion (I/R), this study was carried out to examine the effects of vanadate on I/R-induced changes in cardiac performance and sarcoplasmic reticulum (SR) function. For this purpose, isolated rat hearts were subjected to global ischemia for 30 min and then reperfused for 30 min with normal perfusion medium in the absence or presence of different concentrations of vanadate. The left ventricular developed pressure, rate of contraction and rate of relaxation were depressed, whereas the left ventricular end-diastolic pressure was increased in the ischemic-reperfused heart. However, these abnormalities were attenuated on treatment of the heart with 1 μM and 4 μM of vanadate. The SR preparation isolated from the ischemic-reperfused hearts showed a marked depression in calcium uptake and ryanodine binding (calcium release channel) activities; these defects were attenuated by the addition of vanadate to the perfusion medium. The results demonstrate beneficial effects of vanadate on cardiac dysfunction and changes in SR calcium transport due to I/R injury.

Journal of Pharmacology and Experimental Therapeutics, Apr 1, 2000

Although β-adrenoceptor (β-AR) blockers are used for the treatment of ischemic heart disease, the... more Although β-adrenoceptor (β-AR) blockers are used for the treatment of ischemic heart disease, the mechanisms of their beneficial actions have not been fully elucidated. In view of the role of sarcoplasmic reticular (SR) abnormalities in cardiac dysfunction due to ...

Regulation of Ca2+-ATPases,V-ATPases and F-ATPases, 2015

J Appl Physiol, 2006

To examine whether cardiac hypertrophy is associated with changes in β-adrenoceptor signal transd... more To examine whether cardiac hypertrophy is associated with changes in β-adrenoceptor signal transduction mechanisms, pressure overload (PO) was induced by occlusion of the abdominal aorta and volume overload (VO) by creation of an aortocaval shunt for 4 and 24 wk in rats. After hemodynamic assessment of the animals, the left ventricular (LV) particulate fraction was isolated for measurement of β1-adrenoceptors and adenylyl cyclase activity, and cardiomyocytes were isolated for monitoring of the intracellular Ca2+ concentration. Although PO and VO produced cardiac hypertrophy and increased LV end-diastolic pressure at 4 wk, cardiac function was increased in animals subjected to PO but remained unaltered in animals subjected to VO. Cardiac hypertrophy and increased LV end-diastolic pressure were associated with depressed cardiac function at 24 wk of PO or VO, but clinical signs of congestive heart failure were evident only in animals subjected to VO. Isoproterenol-induced increases in cardiac function, activation of adenylyl cyclase activity, and increase in intracellular Ca2+ concentration, as well as β1-adrenoceptor density, were unaltered by PO at 4 wk, augmented by VO at 4 wk, and attenuated by PO and VO at 24 wk. These results suggest that alterations in β1-adrenoceptor signal transduction are dependent on the type and stage of cardiac hypertrophy.

Experimental and Clinical Cardiology, Feb 1, 2003

BACKGROUND:Mitogen-activated protein kinases (MAPKs) are involved in the regulation of various ce... more BACKGROUND:Mitogen-activated protein kinases (MAPKs) are involved in the regulation of various cellular responses including cell proliferation, differentiation and survival. Although MAPKs are activated by MAPK kinase and inactivated by phosphatases, different types of MAPKs, including extracellular signal-regulated kinases (ERK1 and 2), c-jun N-terminal protein kinases (JNK) and p38 kinases are known to participate in different signalling pathways. This article will review some salient features of the regulation and function of different forms of MAPKs in the heart. Furthermore, the status of cardiac MAPKs under different pathophysiological conditions will be described.OBSERVATIONS:A wide variety of external stimuli are known to activate MAPKs, which are then translocated from the cytoplasm to the nucleus and regulate cardiac gene expression by phosphorylating various transcriptional factors. By virtue of the involvement of ERK1/2 in hypertrophic response and of the stress-activated JNKs and p38 kinases in the process of apoptosis, MAPKs are considered to be intimately involved in cardiac remodelling. Both growth factors and phorbol esters have been shown to strongly activate ERK1/2, whereas the activation of JNKs and p38 kinases by these agents is weak. Although ischemia-reperfusion activates all types of MAPKs, JNKs and p38 kinases are mainly proapoptotic, whereas ERK1/2 are antiapoptotic.CONCLUSIONS:The activation of ERK1/2 is involved in signal transduction pathways associated with cardiac hypertrophy; however, the exact status of MAPKs in heart failure remains to be clearly defined. While both JNKs and p38 kinases appear to participate in the genesis of ischemia-reperfusion injury, ERK1/2 are considered to be cytoprotective.

Journal of Cardiovascular Pharmacology and Therapeutics, 2010

Cardiac Energy Metabolism in Health and Disease, 2014

Developments in Cardiovascular Medicine, 1996

Role of Proteases in Cellular Dysfunction, 2013

Proteases in Health and Disease, 2013