Protein Kinase C and Myocardial Biology and Function
2000; Lippincott Williams & Wilkins; Volume: 86; Issue: 11 Linguagem: Inglês
10.1161/01.res.86.11.1104
ISSN1524-4571
Autores Tópico(s)Cardiac Fibrosis and Remodeling
ResumoHomeCirculation ResearchVol. 86, No. 11Protein Kinase C and Myocardial Biology and Function Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessEditorialPDF/EPUBProtein Kinase C and Myocardial Biology and Function Keiko Naruse and George L. King Keiko NaruseKeiko Naruse From the Joslin Diabetes Center, Research Division, Harvard Medical School, Boston, Mass. and George L. KingGeorge L. King From the Joslin Diabetes Center, Research Division, Harvard Medical School, Boston, Mass. Originally published9 Jun 2000https://doi.org/10.1161/01.RES.86.11.1104Circulation Research. 2000;86:1104–1106Activation of protein kinase C (PKC) and its various isoforms has been postulated to have multiple cardiovascular functions, including vascular permeability, cell migration and growth, extracellular matrix production, and expression of various cytokines.12 The ability of PKC to regulate many cardiovascular functions is not surprising, because PKC, a family of serine-threonine kinases, is an intracellular signal for many cardiovasotropic growth factors, such as angiotensin, endothelin, and vascular endothelial growth and permeability factor.345 In addition, PKC activation can indirectly modulate other signal pathways, such as the Raf-MEK1–MAP kinase and PI3 kinase–Akt cascades.67The physiological importance of PKC can also be surmised by the existence of multiple isoforms, of which 12 members have been documented to date. These are usually arranged according to their structure and substrate requirements into the following groups: conventional PKCs (cPKCs) (α, β1/2, and γ), which are Ca2+ dependent and activated by binding to diacylglycerol (DAG) and phosphatidylserine (PS); novel PKCs (nPKCs) (δ, ε, η, and θ), which are Ca2+ independent but are activated by DAG and PS; and atypical PKCs (aPKCs) (ζ and ι/λ), which are Ca2+ and DAG independent but are PS sensitive. The distribution of the various PKC isoforms is tissue and species dependent. In the heart, PKC isoforms α, β1/2, δ, ε, and ζ have been identified in rat neonatal cardiomyocytes.8 In adult rat cardiomyocytes and myocardium, PKC isoforms δ and ε seem to be maintained with age, whereas other PKC isoforms may decline.910 In human myocardium, PKC isoforms α, β1/2, δ, and ε have also been reported.11 Similarly, all PKC isoforms with the exception of PKCγ have been identified in the microvessels and macrovessels.That the various PKC isoforms have specific cellular or cardiovascular functions is suggested by their specific intracellular locations and apparent preferential activation in response to hormonal or biological stimuli. For example, PKCβ2 is associated with fibrillar structures in unstimulated rat cardiomyocytes and translocates to the perinuclear and plasma membranes on activation.8 PKCβ1 translocates from the cytosol and perinuclear regions into the nucleus when activated. In contrast, PKCδ and PKCε are reported to localize to the perinucleus and nucleus at basal state and translocate to the fibrillar cytoskeletal and cross-striated structures when activated.Changes in specific PKC isoforms located in the myocardium have also been reported, particularly in ischemic preconditioning, ischemia-reperfusion, heart failure due to cardiomyopathy, and diabetes.11121314 The exact PKC isoforms that are preferentially activated in these conditions have been difficult to determine. To date, PKCε and PKCδ are believed to be important for ischemic preconditioning, and PKCα and PKCβ1/2 are activated in heart failure associated with diabetes or nonviral cardiomyopathy. Difficulties in determining the involvement of specific PKC isoforms exist, because PKC activation, as measured by immunoblot analysis to assess translocation, provides only indirect evidence of activation and often does not reflect the extent of activation quantitatively.To determine the specific biological effects of each PKC isoform, several laboratories have used transgenic animals that overexpress or have one PKC isoform deleted in a general or tissue-specific manner (Table). PKCβ-null mice exhibited mild immunological dysfunctions, whereas PKCγ-null mice showed neurological deficit with regard to neuropathic pain.1516Another approach to specifically inhibit or activate a particular PKC isoform has been achieved by manipulating the interaction of the PKC isoforms with their specific anchoring proteins, termed receptors for the activated C kinases (RACKs).17 Much of the information on the RACK protein has been reported by Mochly-Rosen and coworkers. RACKs are 30- to 36 000-Da proteins that are postulated to bind and translocate each PKC isoform. Specific peptide fragments of PKCβ or PKCε introduced into cardiomyocytes have been reported to either activate or inhibit each respective PKC isoform specifically.18192021 Furthermore, PKC peptides derived from PKC RACK-binding or pseudo-RACK sites in cardiomyocytes have been reported to either enhance or abolish ischemic preconditioning, depending on their design.Dorn et al13 previously reported that overexpression of ψεRACK, an analogue of the anchoring and activation protein for PKCε, induced translocation of PKCε in the myocardium. In ψεRACK-overexpressing mice, they showed that PKCε was activated by 20% and the heart was resistant to ischemic injury. In this issue of Circulation Research, Mochly-Rosen et al,22 using an opposite approach, studied the role of PKCε in the heart by inhibiting endogenous PKCε translocation and function by overexpressing an inhibitor of PKCε RACK-binding site (εV1), specifically in the myocardium. They reported that the amount of PKCε in the cardiac particulate fraction decreased by 15% in εV1-overexpressing mice. Their results showed that inhibition of cardiomyocyte PKCε by εV1 induced expression of α-skeletal actin mRNA, increased cardiomyocyte cell size, modestly impaired left ventricular fractional shortening, decreased posterior wall thickness, and, at high levels, caused lethal dilated cardiomyopathy. In contrast, activation of PKCε by ψεRACK was associated with increased β-myosin heavy chain expression, decreased myocyte cell size, increased posterior wall thickness, and normal left ventricular function. These results provide strong evidence that PKCε signaling is important for normal postnatal maturation of myocardial development and ischemic preconditioning. In addition, the results suggest the potential for activation of PKCε as a therapeutic agent for improving cardiac growth and survival after ischemic insult.The role of PKCβ activation has also been defined by overexpressing the PKCβ2 isoform, specifically in the myocardium of mice. Wakasaki et al23 reported myocyte hypertrophy, myocardial necrosis, ventricular thickening, calcification, impaired ventricular systolic performance, and increased expression of atrial natriuretic factor, transforming growth factor-β, collagen types IV and VI, c-fos, and myosin heavy chain-β in PKCβ2-overexpressing mice. Bowman et al24 have also shown that in an inducible model of PKCβ overexpression in the myocardium, adult mice developed ventricular hypertrophy and impaired diastolic relaxation, whereas changes in Ca2+ flux and sudden death were noted in neonatal mice. A specific inhibitor of PKCβ, LY333531, prevented cardiac pathologies in the PKCβ-overexpressing transgenic mice and many other vascular changes in diabetic animals.2326The results of the transgenic animal studies have provided clear and definitive evidence that PKCε has important effects on cardiomyocyte growth and can facilitate the protective responses of ischemic preconditioning.13 In contrast, PKCβ1/2 activation may not be as beneficial, with decreases in cardiac contractility and increases in fibrosis reported. However, many questions remain about the role of other PKC isoforms, such as PKCδ, which is also activated in vivo by diabetes and ischemia.2728 In addition, it is critical to decipher the mechanism by which different PKC isoforms mediate their specific actions in the myocardium and other vascular tissues. For the activation of PKCβ1/2 and PKCε, specificity can be conferred partially by the stimuli. The stimuli that can increase Ca2+ flux will preferentially activate PKCβ1/2. Interestingly, stress-related factors such as ischemia, oxidants, and UV irradiation seem to activate PKCε and stress-related c-Jun NH2-terminal protein kinase and p38 mitogen-activated protein kinase in parallel.293031 However, evidence also indicates that both PKCβ and PKCε can be activated by growth factors, such as epidermal growth factor, and can activate ERK1/2 mitogen-activated protein kinases.32 Thus, it is likely that PKC isoforms have overlapping effects but mediate some of their specific effects via different signaling pathways, which will need to be elucidated to understand important processes such as ischemic preconditioning, myocardial contractility, and growth.From these studies, it is clear that it is no longer adequate to correlate total PKC activity changes with biological or functional changes in the myocardium. It is exciting that molecular approaches have identified functional significance of several PKC isoforms that could be either beneficial or detrimental to cardiac functions. Thus, it should be possible to design specific activators or inhibitors of various PKC isoforms as therapeutic agents to improve cardiac function and potentially decrease myocardial damage from ischemia.The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association. Table 1. Summary of Transgenic Mice Either Overexpressing or Removing a PKC IsoformTissueAuthorsFeaturesKnockoutPKCβ1+β2Whole bodyLeitges et al15Impaired humoral immune responses, reduced cellular responses of B cellsPKCγWhole bodyAbeliovich et al33 Kano et al34 Harris et al35Mild deficits in spatial and contextual learning, impaired synapse elimination during cerebellar development, altered function of GABA receptorsPKCεWhole bodyHodge et al36Supersensitivity of GABA receptors to ethanol and allosteric modulatorsTransgenicPKCβ2HeartWakasaki et al23 Bowman et al24Left ventricular hypertrophy, multifocal fibrosis, impaired diastolic relaxation, abnormalities of Ca2+ fluxPKCβ2IntestineMurray et al37Hyperproliferation, increased sensitivity to colon carcinogenesisPKCδEpidermisReddig et al38Resistant to skin tumor promotion by TPAPKCεEpidermisReddig et al39Enhanced carcinoma formationΨεRACK (PKCε agonist octapeptide)HeartDorn et al13Decreased myocyte cell size, increased posterior wall thickness, cardioprotection from ischemiaεV1 (PKCε pseudosubstrate)HeartMochly-Rosen et al22Increased cardiomyocyte cell size, modestly impaired left ventricular fractional shortening, decreased posterior wall thickness, lethal dilated cardiomyopathy at high levels of εV1GABA indicates γ-aminobutyric acid; TPA, 12-O-tetradecanoylphorbol-13-acetate.FootnotesCorrespondence to George L. King, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215. E-mail [email protected] References 1 Lynch JJ, Ferro TJ, Blumenstock FA, Brockenauer AM, Malik AM. Increased endothelial albumin permeability mediated by protein kinase C activation. J Clin Invest.1990; 85:1991–1998.CrossrefMedlineGoogle Scholar2 Koya D, Jirosek MR, Lin Y-W, Ishi H, Kuboki K, King GL. Characteristics of protein kinase C β isoform activation on the gene expression of transforming growth factor β, extracellular matrix components and prostanoids in the glomeruli of diabetic rats. J Clin Invest.1997; 100:115–126.CrossrefMedlineGoogle Scholar3 Xia P, Aiello LP, Ishii H, Jiang Z, Park DJ, Robinson GS, Takagi H, Newsome WP, Jirousek MR, King GL. Characterization of vascular endothelial growth factor's effect on the activation of protein kinase C, its isoforms, and endothelial cell growth. J Clin Invest.1996; 98:2018–2026.CrossrefMedlineGoogle Scholar4 Takagi C, Bursell S-E, Lin Y-W, Takagi H, Duh E, Jiang Z, Clermont AC, King GL. Regulation of retinal hemodynamics in diabetic rats by increased expression and action of endothelin-1. Invest Ophthalmol Vis Sci.1996; 37:2504–2518.MedlineGoogle Scholar5 Feener EP, Northrup JM, Aiello LP, King GL. Angiotensin II induces plasminogen activator inhibitor-1 and -2 expression in vascular endothelial and smooth muscle cells. J Clin Invest.1995; 95:1353–1362.CrossrefMedlineGoogle Scholar6 Takahashi T, Ueno H, Shibuya M. VEGF activates protein kinase C-dependent, but Ras-independent, Raf-MEK-MAP kinase pathway for DNA synthesis in primary endothelial cells. Oncogene.1999; 18:2221–2230.CrossrefMedlineGoogle Scholar7 Kuboki K, Jiang ZY, Takahara N, Ha SW, Igarashi M, Yamauchi T, Feener EP, Herbert TP, Rhodes CJ, King GL. Regulation of endothelial constitutive nitric oxide synthase gene expression in endothelial cells and in vivo: a specific vascular action of insulin. Circulation..2000; 101:676–681.CrossrefMedlineGoogle Scholar8 Disatnik M-H, Buraggi G, Mochly-Rosen D. Localization of protein kinase C isozymes in cardiac myocytes. Exp Cell Res.1997; 210:287–297.Google Scholar9 Bogoyevitch MA, Parker PJ, Sugden PH. Characterization of protein kinase C isotype expression in adult rat heart: protein kinase C ε is a major isotype present, and it is activated by phorbol esters, epinephrine, and endothelin. Circ Res.1993; 72:757–767.CrossrefMedlineGoogle Scholar10 Rybin VO, Steinberg SF. Protein kinase C isoform expression and regulation in the developing rat heart. Circ Res.1994; 74:299–309.CrossrefMedlineGoogle Scholar11 Bowling N, Walsh RA, Song G, Estridge T, Sandusky GE, Fouts RL, Mintze K, Pickard T, Roden R, Bristow MR, Sabbah HN, Mizrahi JL, Gromo G, King GL, Vlahos CJ. Increased protein kinase C activity and expression of Ca2+-sensitive isoforms in the failing human heart. Circulation.1999; 99:384–391.CrossrefMedlineGoogle Scholar12 Strasser RH, Simonis G, Schon SP, Braun MU, Ihl-Vahl R, Weinbrenner C, Marquetant R, Kubler W. Two distinct mechanisms mediate a differential regulation of protein kinase C isozymes in acute and prolonged myocardial ischemia. Circ Res.1999; 85:77–87.CrossrefMedlineGoogle Scholar13 Dorn GW II, Souroujon MC, Liron T, Chen CH, Gray MO, Zhou HZ, Csukai M, Wu G, Lorenz JN, Mochly-Rosen D. Sustained in vivo cardiac protection by a rationally designed peptide that causes ε protein kinase C translocation. Proc Natl Acad Sci U S A.1999; 96:12798–12803.CrossrefMedlineGoogle Scholar14 Inoguchi T, Battan R, Handler E, Sportsman JR, Heath W, King GL. Preferential elevation of protein kinase C isoform β II and diacylglycerol levels in the aorta and heart of diabetic rats: differential reversibility to glycemic control by islet cell transplantation. Proc Natl Acad Sci U S A.1992; 89:11059–11063.CrossrefMedlineGoogle Scholar15 Leitges M, Schmedt C, Guinamard R, Davoust J, Schaal S, Stabel S, Tarakhovsky A. Immunodeficiency in protein kinase cβ-deficient mice. Science.1996; 273:788–791.CrossrefMedlineGoogle Scholar16 Malmberg AB, Chen C, Tonegawa S, Basbaum AI. Preserved acute pain and reduced neuropathic pain in mice lacking PKCγ. Science.1997; 278:279–283.CrossrefMedlineGoogle Scholar17 Mochly-Rosen D, Khaner H, Lopez J. Identification of intracellular receptor proteins for activated protein kinase C. Proc Natl Acad Sci U S A.1991; 88:3997–4000.CrossrefMedlineGoogle Scholar18 Ron D, Chen C-H, Caldwell J, Jamieson L, Orr E, Mochly-Rosen D. Cloning of an intracellular receptor for protein kinase C: a homolog of the β subunit of G proteins. Proc Natl Acad Sci U S A.1994; 91:839–843.CrossrefMedlineGoogle Scholar19 Csukai M, Chen C-H, De Matteis MA, Mochly-Rosen D. The coatomer protein β′-COP: a selective binding protein (RACK) for protein kinase C ε. J Biol Chem.1997; 272:29200–29206.CrossrefMedlineGoogle Scholar20 Csukai M, Mochly-Rosen D. Pharmacologic modulation of protein kinase C isozymes: the role of RACKs and subcellular localisation. Pharmacol Res.1999; 39:253–259.CrossrefMedlineGoogle Scholar21 Wu HL, Albrightson C, Nambi P. Selective inhibition of rat mesangial cell proliferation by a synthetic peptide derived from the sequence of the C2 region of PKCβ. Peptides.1999; 20:675–678.CrossrefMedlineGoogle Scholar22 Mochly-Rosen D, Wu G, Hahn H, Osinska H, Liron T, Lorenz JN, Yatani A, Robbins J, Dorn GW II. Cardiotrophic effects of protein kinase C ε: analysis by in vivo modulation of PKCε translocation. Circ Res.2000; 86:1182–1188.Google Scholar23 Wakasaki H, Koya D, Schoen FJ, Jirousek MR, Ways DK, Hoit BD, Walsh RA, King GL. Targeted overexpression of protein kinase C β2 isoform in myocardium causes cardiomyopathy. Proc Natl Acad Sci U S A.1997; 94:9320–9325.CrossrefMedlineGoogle Scholar24 Bowman JC, Steinberg SF, Jiang T, Geenen DL, Fishman GI, Buttrick PM. Expression of protein kinase C β in the heart causes hypertrophy in adult mice and sudden death in neonates. J Clin Invest.1997; 100:2189–2195.CrossrefMedlineGoogle Scholar25 Deleted in proof.Google Scholar26 Ishii H, Jirousek MR, Koya D, Takagi C, Xia P, Clermont A, Bursell SE, Kern TS, Ballas LM, Heath WF, Stramm LE, Feener EP, King GL. Amelioration of vascular dysfunctions in diabetic rats by an oral PKCβ inhibitor. Science.1996; 272:728–731.CrossrefMedlineGoogle Scholar27 Koya D, King GL. Protein kinase C activation and the development of diabetic complications. Diabetes.1998; 47:859–866.CrossrefMedlineGoogle Scholar28 Kawamura S, Yoshida K, Miura T, Mizukami Y, Matsuzaki M. Ischemic preconditioning translocates PKC-δ and -ε, which mediate functional protection in isolated rat heart. Am J Physiol.1998; 275:H2266–H2271.MedlineGoogle Scholar29 Chen CH, Gray MO, Mochly-Rosen D. Cardioprotection from ischemia by a brief exposure to physiological levels of ethanol: role of ε protein kinase C. Proc Natl Acad Sci U S A.1999; 96:12784–12789.CrossrefMedlineGoogle Scholar30 Brodie C, Bogi K, Acs P, Lazarovici P, Petrovics G, Anderson WB, Blumberg PM. Protein kinase C-ε plays a role in neurite outgrowth in response to epidermal growth factor and nerve growth factor in PC12 cells. Cell Growth Differ.1999; 10:183–191.MedlineGoogle Scholar31 Ping P, Zhang J, Huang S, Cao X, Tang XL, Li RC, Zheng YT, Qiu Y, Clerk A, Sugden P, Han J, Bolli R. PKC-dependent activation of p46/p54 JNKs during ischemic preconditioning in conscious rabbits. Am J Physiol.1999; 277:H1771–H1785.MedlineGoogle Scholar32 Schonwasser DC, Marais RM, Marshall CJ, Parker PJ. Activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway by conventional, novel, and atypical protein kinase C isotypes. Mol Cell Biol.1998; 18:790–798.CrossrefMedlineGoogle Scholar33 Abeliovich A, Paylor R, Chen C, Kim JJ, Wehner JM, Tonegawa S. PKCγ mutant mice exhibit mild deficits in spatial and contextual learning. Cell.1993; 75:1263–1271.CrossrefMedlineGoogle Scholar34 Kano M, Hashimoto K, Chen C, Abeliovich A, Aiba A, Kurihara H, Watanabe M, Inoue Y, Tonegawa S. Impaired synapse elimination during cerebellar development in PKCγ mutant mice. Cell.1995; 83:1223–1231.CrossrefMedlineGoogle Scholar35 Harris RA, McQuilkin SJ, Paylor R, Abeliovich A, Tonegawa S, Wehner JM. Mutant mice lacking the γ isoform of protein kinase C show decreased behavioral actions of ethanol and altered function of γ-aminobutyrate type A receptors. Proc Natl Acad Sci U S A.1995; 92:3658–3662.CrossrefMedlineGoogle Scholar36 Hodge CW, Mehmert KK, Kelley SP, McMahon T, Haywood A, Olive MF, Wang D, Sanchez-Perez AM, Messing RO. Supersensitivity to allosteric GABA(A) receptor modulators and alcohol in mice lacking PKCε. Nat Neurosci.1999; 2:997–1002.CrossrefMedlineGoogle Scholar37 Murray NR, Davidson LA, Chapkin RS, Clay Gustafson W, Schattenberg DG, Fields AP. Overexpression of protein kinase C βII induces colonic hyperproliferation and increased sensitivity to colon carcinogenesis. J Cell Biol.1999; 145:699–711.CrossrefMedlineGoogle Scholar38 Reddig PJ, Dreckschmidt NE, Ahrens H, Simsiman R, Tseng CP, Zou J, Oberley TD, Verma AK. Transgenic mice overexpressing protein kinase Cδ in the epidermis are resistant to skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate. Cancer Res.1999; 59:5710–5718.MedlineGoogle Scholar39 Reddig PJ, Dreckschmidt NE, Zou J, Bourguignon SE, Oberley TD, Verma AK. Transgenic mice overexpressing protein kinase C ε in their epidermis exhibit reduced papilloma burden but enhanced carcinoma formation after tumor promotion. Cancer Res..2000; 60:595–602.MedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Beattie J, Malavolta M and Korichneva I (2018) Zinc Trace Elements and Minerals in Health and Longevity, 10.1007/978-3-030-03742-0_4, (99-131), . Karuppagounder V, Arumugam S, Giridharan V, Sreedhar R, Bose R, Vanama J, Palaniyandi S, Konishi T, Watanabe K and Thandavarayan R (2017) Tiny molecule, big power: Multi-target approach for curcumin in diabetic cardiomyopathy, Nutrition, 10.1016/j.nut.2016.09.005, 34, (47-54), Online publication date: 1-Feb-2017. Lee J, Yang D, Park J, Kim J, Park W, Cho C and Kim D (2016) MicroRNA-101b attenuates cardiomyocyte hypertrophy by inhibiting protein kinase C epsilon signaling, FEBS Letters, 10.1002/1873-3468.12508, 591:1, (16-27), Online publication date: 1-Jan-2017. Huynh K, Bernardo B, McMullen J and Ritchie R (2014) Diabetic cardiomyopathy: Mechanisms and new treatment strategies targeting antioxidant signaling pathways, Pharmacology & Therapeutics, 10.1016/j.pharmthera.2014.01.003, 142:3, (375-415), Online publication date: 1-Jun-2014. Soetikno V, Sari F, Sukumaran V, Lakshmanan A, Mito S, Harima M, Thandavarayan R, Suzuki K, Nagata M, Takagi R and Watanabe K (2012) Curcumin prevents diabetic cardiomyopathy in streptozotocin-induced diabetic rats: Possible involvement of PKC–MAPK signaling pathway, European Journal of Pharmaceutical Sciences, 10.1016/j.ejps.2012.04.018, 47:3, (604-614), Online publication date: 1-Oct-2012. Wang M, Zhang W, Zhu J, Fu G and Zhou B (2009) Breviscapine ameliorates cardiac dysfunction and regulates the myocardial Ca2+-cycling proteins in streptozotocin-induced diabetic rats, Acta Diabetologica, 10.1007/s00592-009-0164-x, 47:S1, (209-218), Online publication date: 1-Dec-2010. Uenoyama M, Ogata S, Nakanishi K, Kanazawa F, Hiroi S, Tominaga S, Seo A, Matsui T, Kawai T and Suzuki S (2010) Protein kinase C mRNA and protein expressions in hypobaric hypoxia-induced cardiac hypertrophy in rats, Acta Physiologica, 10.1111/j.1748-1716.2009.02064.x, 198:4, (431-440), Online publication date: 1-Apr-2010. Yoshida K (2009) Pursuing enigmas on ischemic heart disease and sudden cardiac death, Legal Medicine, 10.1016/j.legalmed.2008.08.005, 11:2, (51-58), Online publication date: 1-Mar-2009. Wang M, Zhang W, Zhu J, Fu G and Zhou B (2009) Breviscapine ameliorates hypertrophy of cardiomyocytes induced by high glucose in diabetic rats via the PKC signaling pathway, Acta Pharmacologica Sinica, 10.1038/aps.2009.95, 30:8, (1081-1091), Online publication date: 1-Aug-2009. Davidson S, Rybka A and Townsend P (2009) The powerful cardioprotective effects of urocortin and the corticotropin releasing hormone (CRH) family, Biochemical Pharmacology, 10.1016/j.bcp.2008.08.033, 77:2, (141-150), Online publication date: 1-Jan-2009. Min W, Bin Z, Quan Z, Hui Z and Sheng F (2009) The signal transduction pathway of PKC/NF-κB/c-fos may be involved in the influence of high glucose on the cardiomyocytes of neonatal rats, Cardiovascular Diabetology, 10.1186/1475-2840-8-8, 8:1, Online publication date: 1-Dec-2009. Rigor D, Bodyak N, Bae S, Choi J, Zhang L, Ter-Ovanesyan D, He Z, McMullen J, Shioi T, Izumo S, King G and Kang P (2009) Phosphoinositide 3-kinase Akt signaling pathway interacts with protein kinase Cβ2 in the regulation of physiologic developmental hypertrophy and heart function, American Journal of Physiology-Heart and Circulatory Physiology, 10.1152/ajpheart.00562.2008, 296:3, (H566-H572), Online publication date: 1-Mar-2009. Li D, Yang C, Chen Y, Tian J, Liu L, Dai Q, Wan X and Xie Z (2008) Identification of a PKCε-dependent regulation of myocardial contraction by epicatechin-3-gallate, American Journal of Physiology-Heart and Circulatory Physiology, 10.1152/ajpheart.00785.2007, 294:1, (H345-H353), Online publication date: 1-Jan-2008. Qi Q, Gu H, Yang Y, Lu N, Zhao J, Liu W, Ling H, You Q, Wang X and Guo Q (2008) Involvement of matrix metalloproteinase 2 and 9 in gambogic acid induced suppression of MDA-MB-435 human breast carcinoma cell lung metastasis, Journal of Molecular Medicine, 10.1007/s00109-008-0398-z, 86:12, (1367-1377), Online publication date: 1-Dec-2008. Deschamps A, Zavadzkas J, Murphy R, Koval C, McLean J, Jeffords L, Saunders S, Sheats N, Stroud R and Spinale F (2008) Interruption of endothelin signaling modifies membrane type 1 matrix metalloproteinase activity during ischemia and reperfusion, American Journal of Physiology-Heart and Circulatory Physiology, 10.1152/ajpheart.00918.2007, 294:2, (H875-H883), Online publication date: 1-Feb-2008. Siddiqui R, Harvey K and Zaloga G (2008) Modulation of enzymatic activities by n-3 polyunsaturated fatty acids to support cardiovascular health, The Journal of Nutritional Biochemistry, 10.1016/j.jnutbio.2007.07.001, 19:7, (417-437), Online publication date: 1-Jul-2008. Salazar N, Chen J and Rockman H (2007) Cardiac GPCRs: GPCR signaling in healthy and failing hearts, Biochimica et Biophysica Acta (BBA) - Biomembranes, 10.1016/j.bbamem.2007.02.010, 1768:4, (1006-1018), Online publication date: 1-Apr-2007. Henriksson M, Stenman E, Vikman P and Edvinsson L (2007) Protein kinase C inhibition attenuates vascular ETBreceptor upregulation and decreases brain damage after cerebral ischemia in rat, BMC Neuroscience, 10.1186/1471-2202-8-7, 8:1, Online publication date: 1-Dec-2007. Angeloni C, Maraldi T, Ghelli A, Rugolo M, Leoncini E, Hakim G and Hrelia S (2007) Green Tea Modulates α 1 -Adrenergic Stimulated Glucose Transport in Cultured Rat Cardiomyocytes , Journal of Agricultural and Food Chemistry, 10.1021/jf071188+, 55:18, (7553-7558), Online publication date: 1-Sep-2007. Bouwman R, Musters R, van Beek-Harmsen B, de Lange J, Lamberts R, Loer S and Boer C (2007) Sevoflurane-induced cardioprotection depends on PKC-α activation via production of reactive oxygen species, British Journal of Anaesthesia, 10.1093/bja/aem202, 99:5, (639-645), Online publication date: 1-Nov-2007. Yang S and Hwang J (2007) Ca++ influx is essential for the hypotensive response to arginine vasopressin-induced neuron activation of the area postrema in the rat, Brain Research, 10.1016/j.brainres.2007.06.010, 1163, (56-71), Online publication date: 1-Aug-2007. Spinale F (2007) Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function, Physiological Reviews, 10.1152/physrev.00012.2007, 87:4, (1285-1342), Online publication date: 1-Oct-2007. Eduardo Carreño J, Apablaza F, Paz Ocaranza M and E. Jalil J (2006) Hipertrofia cardiaca: eventos moleculares y celulares, Revista Española de Cardiología, 10.1157/13087900, 59:5, (473-486), Online publication date: 1-May-2006. Almela P, Cerezo M, Milanés M and Laorden M (2006) Role of PKC in regulation of Fos and TH expression after naloxone induced morphine withdrawal in the heart, Naunyn-Schmiedeberg's Archives of Pharmacology, 10.1007/s00210-006-0032-y, 372:5, (374-382), Online publication date: 1-Feb-2006. Kiesecker C, Zitron E, Scherer D, Lueck S, Bloehs R, Scholz E, Pirot M, Kathöfer S, Thomas D, Kreye V, Kiehn J, Borst M, Katus H, Schoels W and Karle C (2005) Regulation of cardiac inwardly rectifying potassium current IK1 and Kir2.x channels by endothelin-1, Journal of Molecular Medicine, 10.1007/s00109-005-0707-8, 84:1, (46-56), Online publication date: 1-Jan-2006. Carreño J, Apablaza F, Ocaranza M and Jalil J (2006) Cardiac Hypertrophy: Molecular and Cellular Events, Revista Española de Cardiología (English Edition), 10.1016/S1885-5857(06)60796-2, 59:5, (473-486), Online publication date: 1-May-2006. Apple K, McLean J, Squires C, Schaeffer B, Sample J, Murphy R, Deschamps A, Leonardi A, Allen C, Hendrick J, Stroud R, Mukherjee R and Spinale F (2006) Differential Effects of Protein Kinase C Isoform Activation in Endothelin-Mediated Myocyte Contractile Dysfunction With Cardioplegic Arrest and Reperfusion, The Annals of Thoracic Surgery, 10.1016/j.athoracsur.2006.03.021, 82:2, (664-671), Online publication date: 1-Aug-2006. Korichneva I (2006) Zinc Dynamics in the Myocardial Redox Signaling Network, Antioxidants & Redox Signaling, 10.1089/ars.2006.8.1707, 8:9-10, (1707-1721), Online publication date: 1-Sep-2006. Zaloga G, Harvey K, Stillwell W and Siddiqui R (2016) Trans Fatty Acids and Coronary Heart Disease , Nutrition in Clinical Practice, 10.1177/0115426506021005505, 21:5, (505-512), Online publication date: 1-Oct-2006. Johnsen D, Kacimi R, Anderson B, Thomas T, Said S and Gerdes A (2005) Protein kinase C isozymes in hypertension and hypertrophy: Insight from SHHF rat hearts, Molecular and Cellular Biochemistry, 10.1007/s11010-005-3781-x, 270:1-2, (63-69), Online publication date: 1-Feb-2005. Cerezo M, Milanés M and Laorden M (2005) Alterations in protein kinase A and different protein kinase C isoforms in the heart during morphine withdrawal, European Journal of Pharmacology, 10.1016/j.ejphar.2005.08.025, 522:1-3, (9-19), Online publication date: 1-Oct-2005. Dorn G and Force T (2005) Protein kinase cascades in the regulation of cardiac hypertrophy, Journal of Clinical Investigation, 10.1172/JCI200524178, 115:3, (527-537), Online publication date: 1-Mar-2005. Wang Y, Haider
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