Identification of the changes in phospholipase C isozymes in ischemic–reperfused rat heart

Asemu, Girma; Tappia, Paramjit S.; Dhalla, Naranjan S.

doi:10.1016/s0003-9861(02)00733-6

Cited by 32 publications

(28 citation statements)

References 42 publications

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“…showing that phospholipase C-y1 protein levels decreased by f40% in DKO mice after adriamycin treatment are consistent with those reported by Asemu et al (32), which showed a 40% decrease of phospholipase C-y1 protein levels, and a 35% decrease of phospholipase C-y1 activities in ischemic hearts. Dent et al (33) also showed similar results in volume-overloaded cardiac tissues.…”

Section: Discussionsupporting

confidence: 91%

“…These results suggested that phospholipase C activity was important in TNF receptor-mediated cardioprotection, and the effects were sustained for at least 3 days, which were confirmed by the effect of U73122 on adriamycin-induced decrease of cardiac contractility. Although there is no clear evidence demonstrating the linear relationship between phospholipase C-y1 activities and cardiac function in the literature, Asemu et al (32) have shown that there was f40% decrease of phospholipase C activities and phospholipase C-y1 protein levels (the same decreased levels we observed in adriamycin-treated DKO mice) in the ischemic heart, which corresponded to the significant decreases of cardiac function. Tappia et al (37) also showed that a 30% decrease of phospholipase C activity corresponded with significant decreases in the cardiac function in the diabetic cardiomyopathic rat model.…”

Section: Discussionsupporting

confidence: 65%

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Phospholipase C-δ1 Is a Critical Target for Tumor Necrosis Factor Receptor–Mediated Protection against Adriamycin-Induced Cardiac Injury

Lien¹,

Noel²,

Hua

et al. 2006

Cancer Research

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The clinical application of adriamycin, an exceptionally good chemotherapeutic agent, is limited by its dose-related cardiomyopathy. Our recent study showed that tumor necrosis factor-A (TNF-A) receptors mediated cytoprotective signaling against adriamycin-induced mitochondrial injury and cardiomyocyte apoptosis. In the present study, we investigated the potential targets of TNF receptor-mediated cytoprotective signaling by global genome microarray analysis using wildtype and TNF receptor-deficient mice. Microarray analysis revealed that adriamycin treatment induced the downregulation of several mitochondrial functions and energy production-related genes in double TNF receptor-deficient mice, notably, phospholipase C-D1, a protein involved in fatty acid metabolism and calcium regulation. The role of phospholipase C-D1 in TNF receptor-mediated cardioprotection against adriamycin-induced injury was evaluated by measuring changes in cardiac function using high-frequency ultrasound biomicroscopy. Selective inhibition of phospholipase C activity in wild-type mice by its inhibitor, U73122, exacerbated adriamycin-induced cardiac dysfunction. Inhibition of phospholipase C-D1 resulted in the significant decrease of left ventricular ejection fraction and fractional shortening, and the decreased levels were similar to those observed in adriamycin-treated double TNF receptor-deficient mice. The data derived from the global genome analysis identified phospholipase C-D1 as an important target for TNF receptors and revealed the critical role of TNF receptor signaling in the protection against adriamycin-induced cardiotoxicity. (Cancer Res 2006; 66(8): 4329-38)

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 65%

Phospholipase C-δ1 Is a Critical Target for Tumor Necrosis Factor Receptor–Mediated Protection against Adriamycin-Induced Cardiac Injury

Lien¹,

Noel²,

Hua

et al. 2006

Cancer Research

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“…All experimental protocols for animal studies were approved by the Animal Care Committee of the University of Manitoba, following the guidelines established by the Canadian Council on Animal Care. Heart perfusion and assessment of cardiac performance were conducted as previously described (1). Briefly, male Sprague-Dawley rats weighing 250 -300 g were anesthetized with a mixture of ketamine (60 mg/kg) and xylazine (10 mg/kg).…”

Section: Methodsmentioning

confidence: 99%

“…A small aliquot (1 ml) of the resultant supernatant was centrifuged at 110,000 g (60 min, 4°C), and the resulting supernatant was frozen and stored (Ϫ80°C) as the cytosolic fraction. The rest of the first supernatant was diluted to 30 ml with 300 mM KCl, containing 20 mM MOPS/KOH, pH 7.4, to solubilize myofibrillar proteins, and further processed for the preparation of SL according to the method used previously (1,41,44). The final pellet was resuspended in 0.25 M sucrose and 10 mM histidine (pH 7.4), frozen in liquid N 2, and stored at Ϫ80°C until assayed.…”

Section: Methodsmentioning

confidence: 99%

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Inhibition of PLC improves postischemic recovery in isolated rat heart

Asemu

Dhalla

Tappia

2004

American Journal of Physiology-Heart and Circulatory Physiology

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Asemu, Girma, Naranjan S. Dhalla, and Paramjit S. Tappia. Inhibition of PLC improves postischemic recovery in isolated rat heart. Am J Physiol Heart Circ Physiol 287: H2598 -H2605, 2004. First published August 5, 2004; doi:10.1152/ajpheart.00506.2004The Ca 2ϩ -dependent PLC converts phosphatidylinositol 4,5-bisphosphate to diacylglycerol (DAG) and inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. Because these products modulate Ca 2ϩ movements in the myocardium, PLC may also contribute to a self-perpetuating cycle that exacerbates cardiomyocyte Ca 2ϩ -overload and subsequent cardiac dysfunction in ischemia-reperfusion (I/R). Although we have reported that I/R-induced changes in PLC isozymes might contribute to cardiac dysfunction, the present study was undertaken to examine the beneficial effects of the PLC inhibitor, U-73122, as well as determining the role of Ca 2ϩ on the I/R-induced changes in PLC isozymes. Isolated rat hearts were subjected to global ischemia 30 min, followed by 5 or 30 min of reperfusion. Pretreatment of hearts with U-73122 (0.5 M) significantly inhibited DAG and Ins(1,4,5)P3 production in I/R and was associated with enhanced recovery of cardiac function as indicated by measurement of left ventricular (LV) end-diastolic pressure (EDP), LV diastolic pressure (LVDP), maximum rate of pressure development (ϩdP/dtmax), and maximum rate of LV pressure decay (ϪdP/dtmax). Verapamil (0.1 M) partially prevented the increase in sarcolemmal (SL) PLC-␤1 activity in ischemia and the decrease in its activity during the reperfusion phase as well as elicited a partial protection of the depression in SL PLC-␦1 and PLC-␥1 activities during the ischemic phase and attenuated the increase during the reperfusion period. Although these changes were associated with an improved myocardial recovery after I/R, verapamil was less effective than U-73122. Perfusion with high Ca 2ϩ resulted in the activation of the PLC isozymes studied and was associated with a markedly increased LVEDP and reduced LVDP, ϩdP/dt max, and ϪdP/dt max. These results suggest that inhibition of PLC improves myocardial recovery after I/R. sarcolemma; U-73122; verapamil; hemodynamics THE PHOSPHOINOSITIDE-SPECIFIC PLC isozymes associated with the cardiac sarcolemmal (SL) membrane play an important role in activating intracellular signal transduction pathways for the regulation of various cell functions (4,21,26,34,35). PLC converts its substrate, phosphatidylinositol 4,5-bisphosphate, into two messenger molecules, inositol 1,4,5-trisphosphate [Ins(1,4,5)P 3 ] and 1,2-diacylglycerol (DAG). Whereas Ins(1,4,5)P 3 may serve to enhance the sarcoplasmic reticulum (SR) Ca 2ϩ release (13,19), DAG functions as a potent activator of PKC isozymes which in turn phosphorylate several cardiac proteins (33) and influence Ca 2ϩ movements into the cardiomyocyte (25, 33).Ischemia-reperfusion (I/R) injury is known to occur during clinical procedures, such as coronary bypass surgery, angioplasty, thrombolytic therapy, and cardiac transplantation (3, 6), and has been shown ...

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Phospholipid-Mediated Signaling and Heart Disease

Tappia

Singal²

Subcellular Biochemistry

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Cardiac hypertrophy, congestive heart failure, diabetic cardiomyopathy and myocardial ischemia-reperfusion injury are associated with a disturbance in cardiac sarcolemmal membrane phospholipid homeostasis. The contribution of the different phospholipases and their related signaling mechanisms to altered function of the diseased myocardium is not completely understood. Resolution of this issue is essential for both the understanding of the pathophysiology of heart disease and for determining if components of the phospholipid signaling pathways could serve as appropriate therapeutic targets. This review provides an outline of the role of phospholipase A2, C and D and subsequent signal transduction mechanisms in different cardiac pathologies with a discussion of their potential as targets for drug development for the prevention/treatment of heart disease.

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Identification of the changes in phospholipase C isozymes in ischemic–reperfused rat heart

Cited by 32 publications

References 42 publications

Phospholipase C-δ1 Is a Critical Target for Tumor Necrosis Factor Receptor–Mediated Protection against Adriamycin-Induced Cardiac Injury

Phospholipase C-δ1 Is a Critical Target for Tumor Necrosis Factor Receptor–Mediated Protection against Adriamycin-Induced Cardiac Injury

Inhibition of PLC improves postischemic recovery in isolated rat heart

Phospholipid-Mediated Signaling and Heart Disease

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