Effect of protein kinase C on cerebral ischemic reperfusion injury

Abstract

Abstract: Ischemic stroke is seriously hurting human health because of its high morbidity, disability rate and mortality. The pathophysiology mechanism is very complicated, which involves in expression exchanges of many genes and proteins (sensitive to apoptosis gene, Bcl-2 family proteins, glutathione perodxidase and heat shock protein). Only recombinant tissue plasminogen activator (rtPA) is currently being used in treatment of ischemic stroke by FDA. For multi-factors as inflammation and free radicals, contribute to ischemic stroke, however, many drugs, with few targets and significant side effects, cause a suboptimal therapeutic outcome. So developing new drugs in treatment of ischemic stroke will be an important issue. Some data demonstrated that PKC is likely to involve in mediating ischemic brain injury and may be a promising therapeutic target. Here the role of PKC and PKC isozymes in ischemic reperfusion injury will be discussed.

Key words: Ischemic stroke, PKC, Mechanism, Inflammation, Free radicals

CLC Number:

R743.3

ZHANG Feng-yun, ZHAO Yan, WU Yu-lin. Effect of protein kinase C on cerebral ischemic reperfusion injury[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(4): 461-468.

References

[1] Barone FC, Feuerstein GZ. Inflammatory mediators and stroke: new opportunities for novel therapeutics[J]. J Cereb Blood Flow Metab, 1999, 19(8): 819-834.
[2] Hartings JA, Rolli ML, Lu XC, et al. Delayed secondary phase of peri-infarct depolarizations after focal cerebral ischemia: relation to infarct growth and neuroprotection[J]. J Neurosci, 2003, 23(37): 11602- 11610.
[3] Hai J, Yu F, Lin Q, et al. The changes of signal transduction pathways in hippocampal regions and postsynaptic densities after chronic cerebral hypoperfusion in rats[J]. Brain Res, 2012, 1429(1): 9-17.
[4] 罗慧英, 杨林, 杨焕, 等. 当归挥发油对大鼠局灶性脑缺血再灌注损伤的保护作用[J]. 中国临床药理学与治疗学, 2012, 17(4): 387-391.
[5] 谭婷, 王美纳, 马小亚. 赛庚啶对大鼠脑缺血再灌注损伤的保护作用及对神经细胞凋亡的影响[J]. 中国临床药理学与治疗学, 2011, 16(10): 1096-1100.
[6] Aronowski J, Grotta JC, Strong R, et al. Interplay between the gamma isoform of PKC and calcineurin in regulation of vulnerability to focal cerebral ischemia[J]. J Cereb Blood Flow Metab, 2000, 20(2): 343- 349.
[7] Gao X, Zhang H, Takahashi T, et al. The Akt signaling pathway contributes to postconditioning's protection against stroke; the protection is associated with the MAPK and PKC pathways[J]. J Neurochem, 2008, 105(3): 943-955.
[8] Akimoto K, Takahashi R, Moriya S, et al. EGF or PDGF receptors activate atypical PKClambda through phos-phatidylinositol 3-kinase[J]. EMBO J, 1996, 15(4): 788-798.
[9] Miao Q, Wang S, Miao S, et al. Cardioprotective effect of polydatin against ischemia/reperfusion injury: roles of protein kinase C and mito K(ATP) activation[J]. Phytomedicine, 2011, 19(1): 8-12.
[10] Jiang Q, Gu Z, Zhang G, et al. N-methyl-D-aspartate receptor activation results in regulation of extracellular signal-regulated kinases by protein kinases and phosphatases in glutamate-induced neuronal apototic-like death[J]. Brain Res, 2004, 887(2): 285-292.
[11] Liu C, Peng Z, Zhang N, et al. Identification of differentially expressed microRNAs and their PKC- isoform specific gene network prediction during hypoxic pre-conditioning and focal cerebral ischemia of mice[J]. J Neurochem, 2012, 120(5): 830-841.
[12] Brodie C, Blumberg PM. Regulation of cell apoptosis by protein kinase c delta[J]. Apoptosis, 2003, 8(1): 19-27.
[13] Miettinen S, Roivainen R, Keinänen R, et al. Specific induction of protein kinase C delta subspecies after transient middle cerebral artery occlusion in the rat brain: inhibition by MK-801[J]. J Neurosci, 1996, 16(19): 6236-6245.
[14] Bright R, Raval AP, Dembner JM, et al. Protein kinase C delta mediates cerebral reperfusion injury in vivo[J]. J Neurosci, 2004, 24(31): 6880-6888.
[15] Jean WC, Spellman SR, Nussbaum ES, et al. Reperfusion injury after focal cerebral ischemia: the role of inflammation and the therapeutic horizon[J]. Neurosurgery, 1998, 43(6): 1382-1396.
[16] Cavanagh SP, Gough MJ, Homer-Vanniasinkam S. The role of the neutrophil in ischaemia-reperfusion injury: potential therapeutic interventions[J]. Cardiovasc Surg, 1998, 6(2): 112-118.
[17] Karlsson A, Dahlgren C. Assembly and activation of the neutrophil NADPH oxidase in granule membranes[J]. Antioxid Redox Signal, 2002, 4(1): 49-60.
[18] Chou WH, Choi DS, Zhang H, et al. Neutrophil protein kinase Cdelta as a mediator of stroke- reperfusion injury[J]. J Clin Invest, 2004, 114(1): 49-56.
[19] Walder CE, Green SP, Darbonne WC, et al. Ischemic stroke injury is reduced in mice lacking a functional NADPH oxidase[J]. Stroke, 1997, 28(11): 2252-2258.
[20] Kaminski KA, Bonda TA, Korecki J, et al. Oxidative stress and neutrophil activation-the two keystones of ischemia/reperfusion injury[J]. Int J Cardiol, 2002, 86(1): 41-59.
[21] Shimakura A, Kamanaka Y, Ikeda Y, et al. Neutrophil elastase inhibition reduces cerebral ischemic damage in the middle cerebral artery occlusion[J]. Brain Res, 2000, 858(1): 55-60.
[22] Brown GE, Stewart MQ, Liu H, et al. A novel assay system implicates PtdIns(3,4)P(2), PtdIns(3)P, and PKC delta in intracellular production of reactive oxygen species by the NADPH oxidase[J]. Mol Cell, 2003, 11(1): 35-47.
[23] Fontayne A, Dang PM, Gougerot-Pocidalo MA, et al. Phosphorylation of p47phox sites by PKC alpha, beta II, delta, and zeta: effect on binding to p22phox and on NADPH oxidase activation[J]. Biochemistry, 2002, 41(24): 7743-7750.
[24] Zhu H, Wang Z, Xing Y, et al. Baicalin reduces the permeability of the blood-brain barrier during hypoxia in vitro by increasing the expression of tight junction proteins in brain microvascular endothelial cells[J]. J Ethnopharmacol, 2012, 141(2): 714-720.
[25] Bright R, Steinberg GK, Mochly-Rosen D. DeltaPKC mediates microcerebrovascular dysfunction in acute ischemia and in chronic hypertensive stress in vivo[J]. Brain Res, 2007, 1144: 146-155.
[26] Raval AP, Dave KR, Prado R, et al. Protein kinase C delta cleavage initiates an aberrant signal transduction pathway after cardiac arrest and oxygen glucose deprivation[J]. J Cereb Blood Flow Metab, 2005, 25(6): 730-741.
[27] Akopov SE, Sercombe R, Seylaz J. Endothelial dysfunction in cerebral vessels following carotid artery infusion of phorbol ester in rabbits: the role of polymorphonuclear leukocytes [J]. J Cereb Blood Flow Metab, 1994, 14(6): 1078-1087.
[28] Kaasinen SK, Goldsteins G, Alhonen L, et al. Induction and activation of protein kinase C Delta in hippo- campus and cortex after kainic acid treatment[J]. Exp Neurol, 2002, 176(1): 203-212.
[29] Kheifets V, Bright R, Inagaki K, et al. Protein kinase C delta (deltaPKC)-annexin V interaction: a required step in deltaPKC translocation and function[J]. J Biol Chem, 2006, 281(32): 23218-23226.
[30] Ramzy D, Rao V, Tumiati LC, et al. Elevated endothelin-1 levels impair nitric oxide homeostasis through a PKC-dependent pathway[J]. Circulation, 2006, 114(1 Suppl): I319-I326.
[31] Ikeno F, Inagaki K, Rezaee M, et al. Impaired perfusion after myocardial infarction is due to reperfusion-induced deltaPKC-mediated myocardial damage[J]. Cardiovasc Res, 2007, 73(4): 699-709.
[32] Kanthasamy AG, Kitazawa M, Kanthasamy A, et al. Role of proteolytic activation of protein kinase Cdelta in oxidative stress-induced apoptosis[J]. Antioxid Redox Signal, 2003, 5(5): 609-620.
[33] Inagaki K, Chen L, Ikeno F, et al. Inhibition of delta-protein kinase C protects against reperfusion injury of the ischemic heart in vivo[J]. Circulation, 2003, 108(19): 2304-2307.
[34] Murriel CL, Churchill E, Inagaki K, et al. Protein kinase Cdelta activation induces apoptosis in response to cardiac ischemia and reperfusion damage: a mechanism involving BAD and the mitochondria[J]. J Biol Chem, 2004, 279(46): 47985-47991.
[35] Churchill EN, Szweda LI. Translocation of deltaPKC to mitochondria during cardiac reperfusion enhances superoxide anion production and induces loss in mitochondrial function[J]. Arch Biochem Biophys, 2005, 439(2): 194-199.
[36] Nakane H, Yao H, Ibayashi S, et al. Protein kinase C modulates ischemia-induced amino acids release in the striatum of hypertensive rats[J]. Brain Res, 1998, 782(1/2): 290-296.
[37] Anantharam V, Kitazawa M, Wagner J, et al. Caspase-3-dependent proteolytic cleavage of protein kinase Cdelta is essential for oxidative stress-mediated dopaminergic cell death after exposure to methylcyclopentadienyl manganese tricarbonyl[J]. J Neurosci, 2002, 22(2): 1738-1751.
[38] Dave KR, Bhattacharya SK, Saul I, et al. Activation of protein kinase C delta following cerebral ischemia leads to release of cytochrome C from the mitochondria via bad pathway[J]. PLoS One, 2011, 6(7): e22057.
[39] Friberg H, Wieloch T. Mitochondrial permeability transition in acute neurodegeneration[J]. Biochimie, 2002, 84(2/3): 241-250.
[40] Pérez-Pinzón MA, Basit A, Dave KR, et al. Effect of the first window of ischemic preconditioning on mitochondrial dysfunction following global cerebral ischemia [J]. Mitochondrion, 2002, 2(3): 181-189.
[41] Pérez-Pinzón MA, Sick TJ, Rosenthal M. Mechanism(s) of mitochondrial hyperoxidation after global cerebral ischemia[J]. Adv Exp Med Biol, 1999, 471: 175-180.
[42] Dave KR, Saul I, Busto R, et al. Ischemic preconditioning preserves mitochondrial function after global cerebral ischemia in rat hippocampus [J]. J Cereb Blood Flow Metab, 2001, 21(12): 1401-1410.
[43] Majumder PK, Pandey P, Sun X, et al. Mitochondrial translocation of protein kinase C delta in phorbol ester-induced cytochrome c release and apoptosis[J]. J Biol Chem, 2000, 275(29): 21793-21796.
[44] Haldar S, Basu A, Croce CM. Serine-70 is one of the critical sites for drug-induced Bcl2 phosphorylation in cancer cells[J]. Cancer Res, 1998, 58(8): 1609-1615.
[45] Denning MF, Wang Y, Tibudan S, et al. Caspase activation and disruption of mitochondrial membrane potential during UV radiation-induced apoptosis of human keratinocytes requires activation of protein kinase C [J]. Cell Death Differ, 2002, 9(1): 40-52.
[46] Akita Y. Protein kinase C-epsilon (PKC-epsilon): its unique structure and function [J]. J Biochem, 2002, 132(6): 847-852.
[47] Della-Morte D, Raval AP, Dave KR, et al. Post-ischemic activation of protein kinase C ε protects the hippo-campus from cerebral ischemic injury via alterations in cerebral blood flow [J]. Neurosci Lett, 2011, 487(2): 158-162.
[48] Bright R, Sun GH, Yenari MA, et al. epsilonPKC confers acute tolerance to cerebral ischemic reperfusion injury [J]. Neurosci Lett, 2008, 441(1): 120-124.
[49] Di-Capua N, Sperling O, Zoref-Shani E. Protein kinase C-epsilon is involved in the adenosine- activated signal transduction pathway conferring protection against ischemia-reperfusion injury in primary rat neuronal cultures [J]. J Neurochem, 2003, 84(2): 409-412.
[50] Dorn GW, Souroujon MC, Liron T, et al. Sustained in vivo cardiac protection by a rationally designed peptide that causes epsilon protein kinase C translocation [J]. Proc Natl Acad Sci U S A, 1999, 96(22): 12798-12803.
[51] Li J, Niu C, Han S, et al. Identification of protein kinase C isoforms involved in cerebral hypoxic preconditioning of mice [J]. Brain Res, 2005, 1060(1/2): 62-72.
[52] Wang J, Bright R, Mochly-Rosen D, et al. Cell-specific role for epsilon- and betaI-protein kinase C isozymes in protecting cortical neurons and astrocytes from ischemia-like injury [J]. Neuropharmacology, 2004, 47(1): 136-145.
[53] McNamara RK, Wees EA, Lenox RH. Differential subcellular redistribution of protein kinase C isozymes in the rat hippocampus induced by kainic acid [J]. J Neurochem, 1999, 72(4): 1735-1743.
[54] Kumar K, Wu XL. Post-ischemic changes in protein kinase C RNA in the gerbil brain following prolonged periods of recirculation: a phosphorimaging study [J]. Metab Brain Dis, 1994, 9(4): 323-331.
[55] Lange-Asschenfeldt C, Raval AP, Dave KR, et al. Epsilon protein kinase C mediated ischemic tolerance requires activation of the extracellular regulated kinase pathway in the organotypic hippocampal slice [J]. J Cereb Blood Flow Metab, 2004, 24(6): 636-645.
[56] Teshima Y, Akao M, Li RA, et al. Mitochondrial ATP-sensitive potassium channel activation protects cerebellar granule neurons from apoptosis induced by oxidative stress [J]. Stroke, 2003, 34(7): 1796-1802.
[57] Koponen S, Kurkinen K, Akerman KE, et al. Prevention of NMDA-induced death of cortical neurons by inhibition of protein kinase Czeta [J]. J Neurochem, 2003, 86(2): 442-450.
[58] MacDonald JF, Kotecha SA, Lu WY, et al. Convergence of PKC-dependent kinase signal cascades on NMDA receptors [J]. Curr Drug Targets, 2001, 2(3): 299-312.
[59] Arundine M, Tymianski M. Molecular mechanisms of glutamate-dependent neurodegeneration in ischemia and traumatic brain injury [J]. Cell Mol Life Sci, 2004, 61(6): 657-668.
[60] Kowalczyk JE, Kawalec M, Beresewicz M, et al. Protein kinase C beta in postischemic brain mitochondria [J]. Mitochondrion, 2012, 12(1): 138-143.
[61] Sieber FE, Traystman RJ, Brown PR, et al. Protein kinase C expression and activity after global incomplete cerebral ischemia in dogs [J]. Stroke, 1998, 29(7): 1445-1452.
[62] Aronowski J, Labiche LA. Perspectives on reperfusion-induced damage in rodent models of experimental focal ischemia and role of gamma-protein kinase C [J]. ILAR J, 2003, 44(2): 105-109.