Cardioadaptation Induced by Cyclic Ischemic Preconditioning Is Mediated by Translational Regulation ofde NovoProtein Synthesis

Rowland, Robert T.; Meng, Xianzhong; Cleveland, Joseph C.; Meldrum, Daniel R.; Harken, Alden H.; Brown, James M.

doi:10.1006/jsre.1997.5142

Cited by 32 publications

(21 citation statements)

References 16 publications

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“…Under the experimental conditions employed in this study, we (10,16) previously reported that the recovery in cardiac performance and SR function observed in I/R and CP hearts due to IP were related to the preserved protein content of SR Ca 2ϩ -cycling proteins. However, it is important to mention that the functional recovery of SR proteins may not be linked to the status of their gene expression (18) because the short duration of our experiment (30-min reperfusion) may not be sufficient to impart the expression of the corresponding proteins, and therefore the improvement in gene expression will not result in de novo protein synthesis in the heart. On the other hand, it is likely that IP may rescue the SR protein levels from degradation by Ca 2ϩ -dependent proteases that are activated during I/R (27).…”

Section: Discussionmentioning

confidence: 99%

Preconditioning prevents alterations in cardiac SR gene expression due to ischemia-reperfusion

Temsah

Kawabata

Chapman

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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Temsah, Rana M., Kenichi Kawabata, Donald Chapman, and Naranjan S. Dhalla. Preconditioning prevents alterations in cardiac SR gene expression due to ischemiareperfusion. Am J Physiol Heart Circ Physiol 282: H1461-H1466, 2002; 10.1152/ajpheart.00447.2001.-We have previously shown that ischemic preconditioning (IP) improves cardiac performance and sarcoplasmic reticulum (SR) function in hearts subjected to ischemia-reperfusion (I/R). In this study, we examined the effect of IP on I/R-induced changes in gene expression for SR proteins such as the Ca 2ϩ release channel, Ca 2ϩ pump ATPase, phospholamban, and calsequestrin in the isolated rat heart. Normal isolated rat hearts exposed to three brief cycles of IP (5-min ischemia and 5-min reperfusion) exhibited a significant decrease in the transcript levels of SR genes. Nonpreconditioned I/R hearts when subjected to 30-min ischemia and 30-min reperfusion showed a marked decrease in mRNA levels for the SR proteins compared with normal hearts; this decrease was attenuated by preconditioning. Although hearts subjected to Ca 2ϩ paradox (CP) have been shown to exhibit intracellular Ca 2ϩ overload and SR dysfunction like those in I/R hearts, virtually nothing is known regarding the effect of CP on cardiac SR gene expression. Accordingly, CP (5-min Ca 2ϩ -free perfusion and 30-min reperfusion with normal medium) was observed to produce dramatic changes in SR gene expression, and the heart failed to contract; these alterations were attenuated by IP. Our results show that 1) both I/R and CP depress SR gene expression in the normal heart, 2) IP attenuates I/R-and CP-induced depression in cardiac function and SR gene expression, and 3) intracellular Ca 2ϩ overload may play a role in depressing SR gene expression in both I/R and CP hearts. ischemic preconditioning; ischemia-reperfusion; cardiac mRNA levels; Ca 2ϩ paradoxic heart ISCHEMIC PRECONDITIONING (IP) was first defined by Murry et al. (14) as repetitive cycles of brief ischemia and reperfusion that protected the heart against a subsequent period of prolonged ischemic injury. IP has been shown to enhance the recovery of cardiac function (4, 16), decrease the incidence of arrhythmias (8,19), and reduce infarct size (8) in hearts subjected to ischemia-reperfusion (I/R) injury. Several endogenous mediators such as adenosine, norepinephrine, protein kinase C, and free radicals have been proposed to mediate the beneficial effects of IP (11). Earlier, we (9) reported that IP improved cardiac performance not only in hearts exposed to I/R (16) but also in hearts subjected to Ca 2ϩ paradox (CP). CP is known to occur as a consequence of a brief period of Ca 2ϩ depletion followed by Ca 2ϩ repletion (28) and is considered to be an appropriate model for studying the effect of intracellular Ca 2ϩ overload as a contributing factor in the pathogenesis of cardiac dysfunction (1, 2).By virtue of its ability to regulate the intracellular concentration of free Ca 2ϩ , the sarcoplasmic reticulum (SR) plays a central role in the cardiac contracti...

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Section: Discussionmentioning

confidence: 99%

Preconditioning prevents alterations in cardiac SR gene expression due to ischemia-reperfusion

Temsah

Kawabata

Chapman

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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“…However, acute changes in gene expression occur during ischemia-reperfusion (120,183) and with protective stimuli (46, 51, 198), and there is support for roles for de novo protein synthesis and/or gene transcription in acute protection with preconditioning (199,241,268). Several studies provide intriguing, if not compelling, support for a transcriptional component in acute adenosinergic protection (120,266).…”

Section: Are Acute Effects Of Adenosine Receptor Activation Entirely mentioning

confidence: 99%

Acute adenosinergic cardioprotection in ischemic-reperfused hearts

Headrick

Hack

Ashton

2003

American Journal of Physiology-Heart and Circulatory Physiology

150

164

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. Acute adenosinergic cardioprotection in ischemic-reperfused hearts. Am J Physiol Heart Circ Physiol 285: H1797-H1818, 2003; 10.1152/ajpheart.00407. 2003.-Cells of the cardiovascular system generate and release purine nucleoside adenosine in increasing quantities when constituent cells are "stressed" or subjected to injurious stimuli. This increased adenosine can interact with surface receptors in myocardial, vascular, fibroblast, and inflammatory cells to modulate cellular function and phenotype. Additionally, adenosine is rapidly reincorporated back into 5Ј-AMP to maintain the adenine nucleotide pool. Via these receptor-dependent and independent (metabolic) paths, adenosine can substantially modify the acute response to ischemic insult, in addition to generating a more sustained ischemia-tolerant phenotype (preconditioning). However, the molecular basis for acute adenosinergic cardioprotection remains incompletely understood and may well differ from more widely studied preconditioning. Here we review current knowledge and some controversies regarding acute cardioprotection via adenosine and adenosine receptor activation.adenosine; adenosine receptor activation; ischemia; reperfusion injury THE HEART possesses its own intrinsic protective responses, including the adenosine receptor system, which enhance resistance to ischemic insult. An understanding of the mechanisms involved in these responses not only informs us of how the heart reacts to injurious stimuli, but may provide avenues for developing novel protective strategies applicable in the setting of ischemia-reperfusion. The purine nucleoside adenosine was attributed with cardioregulatory functions almost 75 years ago (64), and since then has emerged as a crucially important control substance in essentially every tissue of the body. In the heart adenosine not only plays a role in regulating growth and differentiation, angiogenesis, coronary blood flow, cardiac conduction and heart rate, substrate metabolism, and sensitivity to adrenergic stimulation (23,67,68,73,74,260,271,283), but may play a role as an endogenous determinant of ischemic tolerance (189,225,245,259,311,312,318). From a therapeutic viewpoint, adenosine-based therapies protect against ischemic injury in a variety of animal models (72,177,208,265,288) and in human cardiac tissue (34, 36, 37,240,296). However, much remains unclear regarding the roles and mechanisms of action of adenosine in producing acute protection against ischemia and reperfusion. Generation of Endogenous Adenosine During InsultEndogenous adenosine levels increase rapidly with ischemic insult (104,109,285,286) to mediate a retaliatory response. This protective pool of adenosine can be formed via dephosphorylation of 5Ј-AMP by intra-and extracellular 5Ј-nucleotidases and from S-adenosylhomocysteine (SAH) via SAH hydrolase. Extracellular adenosine is rapidly taken into cells via a facilitative transporter (131). Within cells it is either deaminated by adenosine deaminase or rephosphorylated to 5Ј-AMP via adenosine kinase. O...

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“…Experimentally, it is the most powerful form of cardiac protection known and it has been demonstrated in cardiac myocytes [2][3][4][5], intact hearts [6,7] and many animal species [8][9][10][11], including humans [12][13][14]. Downstream signalling molecules reported to be involved in PC include ATPdependent potassium channels [4,12,15,16], PKC (protein kinase C) isoenzymes [2, 3,12,15,17,18], MAPK (mitogen-activated protein kinase) enzymes [19][20][21], tyrosine kinases [22][23][24], PI3K (phosphoinositide 3-kinase) [22,25], heat-shock proteins [5,16,26], nitric oxide [27][28][29], free radicals [21,25,30] etc.…”

Section: Introductionmentioning

confidence: 99%

Protein kinase Cϵ interacts with cytochrome c oxidase subunit IV and enhances cytochrome c oxidase activity in neonatal cardiac myocyte preconditioning

Ogbi

Johnson

2005

Biochemical Journal

117

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We have previously identified a phorbol ester-induced PKCϵ (protein kinase Cϵ) interaction with the (∼18 kDa) COIV [CO (cytochrome c oxidase) subunit IV] in NCMs (neonatal cardiac myocytes). Since PKCϵ has been implicated as a key mediator of cardiac PC (preconditioning), we examined whether hypoxic PC could induce PKCϵ–COIV interactions. Similar to our recent study with phorbol esters [Ogbi, Chew, Pohl, Stuchlik, Ogbi and Johnson (2004) Biochem. J. 382, 923–932], we observed a time-dependent increase in the in vitro phosphorylation of an approx. 18 kDa protein in particulate cell fractions isolated from NCMs subjected to 1–60 min of hypoxia. Introduction of a PKCϵ-selective translocation inhibitor into cells attenuated this in vitro phosphorylation. Furthermore, when mitochondria isolated from NCMs exposed to 30 min of hypoxia were subjected to immunoprecipitation analyses using PKCϵ-selective antisera, we observed an 11.1-fold increase in PKCϵ–COIV co-precipitation. In addition, we observed up to 4-fold increases in CO activity after brief NCM hypoxia exposures that were also attenuated by introducing a PKCϵ-selective translocation inhibitor into the cells. Finally, in Western-blot analyses, we observed a >2-fold PC-induced protection of COIV levels after 9 h index hypoxia. Our studies suggest that a PKCϵ–COIV interaction and an enhancement of CO activity occur in NCM hypoxic PC. We therefore propose novel mechanisms of PKCϵ-mediated PC involving enhanced energetics, decreased mitochondrial reactive oxygen species production and the preservation of COIV levels.

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Cardioadaptation Induced by Cyclic Ischemic Preconditioning Is Mediated by Translational Regulation ofde NovoProtein Synthesis

Cited by 32 publications

References 16 publications

Preconditioning prevents alterations in cardiac SR gene expression due to ischemia-reperfusion

Preconditioning prevents alterations in cardiac SR gene expression due to ischemia-reperfusion

Acute adenosinergic cardioprotection in ischemic-reperfused hearts

Protein kinase Cϵ interacts with cytochrome c oxidase subunit IV and enhances cytochrome c oxidase activity in neonatal cardiac myocyte preconditioning

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