Role of Calcium-independent Phospholipase A2beta in High Glucose-induced Activation of RhoA, Rho Kinase, and CPI-17 in Cultured Vascular Smooth Muscle Cells and Vascular Smooth Muscle Hypercontractility in Diabetic Animals

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2010 Jan 21

PMID 20086008

Citations 37

Authors

Zhongwen Xie

Ming C Gong

Wen Su

Dongping Xie

John Turk

Zhenheng Guo

Affiliations

Soon will be listed here.

Abstract

Previous studies suggest that high glucose-induced RhoA/Rho kinase/CPI-17 activation is involved in diabetes-associated vascular smooth muscle hypercontractility. However, the upstream signaling that links high glucose and RhoA/Rho kinase/CPI-17 activation is unknown. Here we report that calcium-independent phospholipase A(2)beta (iPLA(2)beta) is required for high glucose-induced RhoA/Rho kinase/CPI-17 activation and thereby contributes to diabetes-associated vascular smooth muscle hypercontractility. We demonstrate that high glucose increases iPLA(2)beta mRNA, protein, and iPLA(2) activity in a time-dependent manner. Protein kinase C is involved in high glucose-induced iPLA(2)beta protein up-regulation. Inhibiting iPLA(2)beta activity with bromoenol lactone or preventing its expression by genetic deletion abolishes high glucose-induced RhoA/Rho kinase/CPI-17 activation, and restoring expression of iPLA(2)beta in iPLA(2)beta-deficient cells also restores high glucose-induced CPI-17 phosphorylation. Pharmacological and genetic inhibition of 12/15-lipoxygenases has effects on high glucose-induced CPI-17 phosphorylation similar to iPLA(2)beta inhibition. Moreover, increases in iPLA(2) activity and iPLA(2)beta protein expression are also observed in both type 1 and type 2 diabetic vasculature. Pharmacological and genetic inhibition of iPLA(2)beta, but not iPLA(2)gamma, diminishes diabetes-associated vascular smooth muscle hypercontractility. In summary, our results reveal a novel mechanism by which high glucose-induced, protein kinase C-mediated iPLA(2)beta up-regulation activates the RhoA/Rho kinase/CPI-17 via 12/15-lipoxygenases and thereby contributes to diabetes-associated vascular smooth muscle hypercontractility.

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References

McHowat J, Creer M, Hicks K, Jones J, McCrory R, Kennedy R . Induction of Ca-independent PLA(2) and conservation of plasmalogen polyunsaturated fatty acids in diabetic heart. Am J Physiol Endocrinol Metab. 2000; 279(1):E25-32. DOI: 10.1152/ajpendo.2000.279.1.E25. View

Bolick D, Srinivasan S, Whetzel A, Fuller L, Hedrick C . 12/15 lipoxygenase mediates monocyte adhesion to aortic endothelium in apolipoprotein E-deficient mice through activation of RhoA and NF-kappaB. Arterioscler Thromb Vasc Biol. 2006; 26(6):1260-6. DOI: 10.1161/01.ATV.0000217909.09198.d6. View

Pang H, Guo Z, Xie Z, Su W, Gong M . Divergent kinase signaling mediates agonist-induced phosphorylation of phosphatase inhibitory proteins PHI-1 and CPI-17 in vascular smooth muscle cells. Am J Physiol Cell Physiol. 2005; 290(3):C892-9. DOI: 10.1152/ajpcell.00378.2005. View

Xie Z, Gong M, Su W, Turk J, Guo Z . Group VIA phospholipase A2 (iPLA2beta) participates in angiotensin II-induced transcriptional up-regulation of regulator of g-protein signaling-2 in vascular smooth muscle cells. J Biol Chem. 2007; 282(35):25278-89. PMC: 2096773. DOI: 10.1074/jbc.M611206200. View

Xie Z, Su W, Guo Z, Pang H, Post S, Gong M . Up-regulation of CPI-17 phosphorylation in diabetic vasculature and high glucose cultured vascular smooth muscle cells. Cardiovasc Res. 2005; 69(2):491-501. DOI: 10.1016/j.cardiores.2005.11.002. View

Balsinde J, Balboa M, Insel P, Dennis E . Regulation and inhibition of phospholipase A2. Annu Rev Pharmacol Toxicol. 1999; 39:175-89. DOI: 10.1146/annurev.pharmtox.39.1.175. View

Park K, Trucillo M, Serban N, Cohen R, Bolotina V . Role of iPLA2 and store-operated channels in agonist-induced Ca2+ influx and constriction in cerebral, mesenteric, and carotid arteries. Am J Physiol Heart Circ Physiol. 2007; 294(3):H1183-7. DOI: 10.1152/ajpheart.01148.2007. View

Akiba S, Ohno S, Chiba M, Kume K, Hayama M, Sato T . Protein kinase Calpha-dependent increase in Ca2+-independent phospholipase A2 in membranes and arachidonic acid liberation in zymosan-stimulated macrophage-like P388D1 cells. Biochem Pharmacol. 2002; 63(11):1969-77. DOI: 10.1016/s0006-2952(02)00988-7. View

Muller A, Schott-Ohly P, Dohle C, Gleichmann H . Differential regulation of Th1-type and Th2-type cytokine profiles in pancreatic islets of C57BL/6 and BALB/c mice by multiple low doses of streptozotocin. Immunobiology. 2002; 205(1):35-50. DOI: 10.1078/0171-2985-00109. View

10.

Guo Z, Su W, Allen S, Pang H, Daugherty A, Smart E . COX-2 up-regulation and vascular smooth muscle contractile hyperreactivity in spontaneous diabetic db/db mice. Cardiovasc Res. 2005; 67(4):723-35. DOI: 10.1016/j.cardiores.2005.04.008. View

11.

van Tienhoven M, Atkins J, Li Y, Glynn P . Human neuropathy target esterase catalyzes hydrolysis of membrane lipids. J Biol Chem. 2002; 277(23):20942-8. DOI: 10.1074/jbc.M200330200. View

12.

Bao S, Miller D, Ma Z, Wohltmann M, Eng G, Ramanadham S . Male mice that do not express group VIA phospholipase A2 produce spermatozoa with impaired motility and have greatly reduced fertility. J Biol Chem. 2004; 279(37):38194-200. PMC: 3733543. DOI: 10.1074/jbc.M406489200. View

13.

Nobe K, Sakai Y, Maruyama Y, Momose K . Hyper-reactivity of diacylglycerol kinase is involved in the dysfunction of aortic smooth muscle contractility in streptozotocin-induced diabetic rats. Br J Pharmacol. 2002; 136(3):441-51. PMC: 1573360. DOI: 10.1038/sj.bjp.0704722. View

14.

Fuentes L, Perez R, Nieto M, Balsinde J, Balboa M . Bromoenol lactone promotes cell death by a mechanism involving phosphatidate phosphohydrolase-1 rather than calcium-independent phospholipase A2. J Biol Chem. 2003; 278(45):44683-90. DOI: 10.1074/jbc.M307209200. View

15.

Somlyo A, Somlyo A . Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev. 2003; 83(4):1325-58. DOI: 10.1152/physrev.00023.2003. View

16.

Ma Z, Turk J . The molecular biology of the group VIA Ca2+-independent phospholipase A2. Prog Nucleic Acid Res Mol Biol. 2001; 67:1-33. DOI: 10.1016/s0079-6603(01)67023-5. View

17.

Steer S, Wirsig K, Creer M, Ford D, McHowat J . Regulation of membrane-associated iPLA2 activity by a novel PKC isoform in ventricular myocytes. Am J Physiol Cell Physiol. 2002; 283(6):C1621-6. DOI: 10.1152/ajpcell.00109.2002. View

18.

Lagaud G, Masih-Khan E, Kai S, van Breemen C, Dube G . Influence of type II diabetes on arterial tone and endothelial function in murine mesenteric resistance arteries. J Vasc Res. 2001; 38(6):578-89. DOI: 10.1159/000051094. View

19.

Dennis E . Diversity of group types, regulation, and function of phospholipase A2. J Biol Chem. 1994; 269(18):13057-60. View

20.

Shimokawa H, Takeshita A . Rho-kinase is an important therapeutic target in cardiovascular medicine. Arterioscler Thromb Vasc Biol. 2005; 25(9):1767-75. DOI: 10.1161/01.ATV.0000176193.83629.c8. View