Heat Shock Transcription Factor 1 Protects Cardiomyocytes From Ischemia/Reperfusion Injury

Zou, Yunzeng; Zhu, Weidong; Sakamoto, Masaya; Qin, Yingjie; Akazawa, Hiroshi; Toko, Haruhiro; Mizukami, Masaaki; Takeda, Norihiko; Minamino, Tohru; Takano, Hiroyuki; Nagai, Toshio; Nakai, Asami; Komuro, Issei

doi:10.1161/01.cir.0000101923.54751.77

Cited by 67 publications

(45 citation statements)

References 36 publications

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“…Recent studies showed the important role of the PI3K-Akt signaling pathway in survival of cardiomyocytes as well as protection against myocardial I/R injury in mice (2,61,71). The antiapoptotic effect of Akt is mediated by direct phosphorylation and inactivation of proapoptotic proteins, including caspase-9, an upstream activator of caspase-3 (18).…”

Section: Discussionmentioning

confidence: 99%

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C-phycocyanin protects against ischemia-reperfusion injury of heart through involvement of p38 MAPK and ERK signaling

Khan¹,

Varadharaj²,

Ganesan³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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pusamy. C-phycocyanin protects against ischemia-reperfusion injury of heart through involvement of p38 MAPK and ERK signaling. Am J Physiol Heart Circ Physiol 290: H2136 -H2145, 2006. First published December 22, 2005 doi:10.1152/ajpheart.01072.2005.-We previously showed that C-phycocyanin (PC), an antioxidant biliprotein pigment of Spirulina platensis (a blue-green alga), effectively inhibited doxorubicininduced oxidative stress and apoptosis in cardiomyocytes. Here we investigated the cardioprotective effect of PC against ischemia-reperfusion (I/R)-induced myocardial injury in an isolated perfused Langendorff heart model. Rat hearts were subjected to 30 min of global ischemia at 37°C followed by 45 min of reperfusion. Hearts were perfused with PC (10 M) or Spirulina preparation (SP, 50 mg/l) for 15 min before the onset of ischemia and throughout reperfusion. After 45 min of reperfusion, untreated (control) hearts showed a significant decrease in recovery of coronary flow (44%), left ventricular developed pressure (21%), and rate-pressure product (24%), an increase in release of lactate dehydrogenase and creatine kinase in coronary effluent, significant myocardial infarction (44% of risk area), and TdT-mediated dUTP nick end labelpositive apoptotic cells compared with the preischemic state. PC or SP significantly enhanced recovery of heart function and decreased infarct size, attenuated lactate dehydrogenase and creatine kinase release, and suppressed I/R-induced free radical generation. PC reversed I/R-induced activation of p38 MAPK, Bax, and caspase-3, suppression of Bcl-2, and increase in TdT-mediated dUTP nick end label-positive apoptotic cells. However, I/R also induced activation of ERK1/2, which was enhanced by PC treatment. Overall, these results for the first time showed that PC attenuated I/R-induced cardiac dysfunction through its antioxidant and antiapoptotic actions and modulation of p38 MAPK and ERK1/2. oxidative stress; apoptosis; Spirulina; antioxidant; reactive oxygen species; free radicals THE HEART IS SUBJECTED to episodes of ischemia, followed by reperfusion, in a number of situations, including angina, myocardial infarction, and cardiac surgery. These stresses can result in cell injury and death. The pathogenesis of myocardial ischemia-reperfusion (I/R) injury involves the interplay of multiple mechanisms. Numerous studies have indicated the role of oxidative damage mediated by activation of xanthine oxidase and subsequent formation of reactive oxygen species (ROS), including O 2 Ϫ ⅐, H 2 O 2 , ⅐OH, and peroxynitrite, lipid peroxidation of myocardial membranes, action of iron, decrease in GSH, altered GSH-to-GSSG ratio, depletion of highenergy phosphates including ATP, depressed energy metabolism, and altered calcium homeostasis in the pathogenesis of

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Section: Discussionmentioning

confidence: 99%

“…Earlier studies demonstrated the activation of ERK1/2 after reperfusion, which is cardioprotective (23,29,41,68). Phosphatidylinositol 3-kinase (PI3K)-Akt signaling is an important mediator of cell survival and promotes survival of cardiomyocytes in vitro and in vivo (2,61,71). In addition, it protects against acute I/R injury in the mouse heart (2,71).…”

mentioning

confidence: 99%

C-phycocyanin protects against ischemia-reperfusion injury of heart through involvement of p38 MAPK and ERK signaling

Khan¹,

Varadharaj²,

Ganesan³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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“…16 By inducing Hsps, heat shock can prevent apoptosis in cardiomyocytes. 17,18 Also, hyperthermia protected mice from tumor necrosis factor 19 and gamma radiation. 20 Yet, heat shock cannot be safely used in patients.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological induction of Hsp70 protects apoptosis-prone cells from doxorubicin: comparison with caspase-inhibitor- and cycle-arrest-mediated cytoprotection

Demidenko

Vivo²,

Halicka

et al. 2005

Cell Death Differ

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Selective modulation of cell death is important for rational chemotherapy. By depleting Hsp90-client oncoproteins, geldanamycin (GA) and 17-allylamino-17-demethoxy-GA (17-AAG) (heat-shock protein-90-active drugs) render certain oncoprotein-addictive cancer cells sensitive to chemotherapy. Here we investigated effects of GA and 17-AAG in apoptosis-prone cells such as HL60 and U937. In these cells, doxorubicin (DOX) caused rapid apoptsis, whereas GAinduced heat-shock protein-70 (Hsp70) (a potent inhibitor of apoptosis) and G1 arrest without significant apoptosis. GA blocked caspase activation and apoptosis and delayed cell death caused by DOX. Inhibitors of translation and transcription and siRNA Hsp70 abrogated cytoprotective effects of GA. Also GA failed to protect HL60 cells from cytotoxicity of actinomycin D and flavopiridol (FL), inhibitors of transcription. We next compared cytoprotection by GA-induced Hsp70, caspase inhibitors (Z-VAD-fmk) and cell-cycle arrest. Whereas cell-cycle arrest protected HL60 cells from paclitaxel (PTX) but not from FL and DOX, Z-VAD-fmk prevented FLinduced apoptosis but was less effective against DOX and PTX. Thus, by inducing Hsp70, GA protected apoptosis-prone cells in unique and cell-type selective manner. Since GA does not protect apoptosis-reluctant cancer cells, we envision a therapeutic strategy to decrease side effects of chemotherapy without affecting its therapeutic efficacy.

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“…Akt promotes the survival of cardiomyocytes in vitro in addition to protection against acute I/Rinduced injury in the mouse heart (4,5). Similarly, our recent study showed that kallikrein gene delivery protects against cerebral ischemia injury and apoptosis along with activation of Akt signaling (6).…”

mentioning

confidence: 99%

Kallikrein/Kinin Protects against Myocardial Apoptosis after Ischemia/Reperfusion via Akt-Glycogen Synthase Kinase-3 and Akt-Bad·14-3-3 Signaling Pathways

Yin

Chao

2005

Journal of Biological Chemistry

109

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Our previous study has shown that human tissue kallikrein protected against ischemia/reperfusion-induced myocardial injury. In the present study, we investigated the protective role of local kallikrein gene delivery in ischemia/reperfusion-induced cardiomyocyte apoptosis and its signaling mechanisms in promoting cardiomyocyte survival. Adenovirus carrying the human tissue kallikrein gene was delivered locally into the heart using a catheter-based technique. Expression and localization of recombinant human kallikrein in rat myocardium after gene transfer were determined immunohistochemically. Kallikrein gene delivery markedly reduced reperfusion-induced cardiomyocyte apoptosis identified by both in situ nick end-labeling and DNA fragmentation. Delivery of the kallikrein gene increased phosphorylation of Src, Akt, glycogen synthase kinase (GSK)-3␤, and Bad(Ser-136) but reduced caspase-3 activation in rat myocardium after reperfusion. The protective effect of kallikrein on apoptosis and its signaling mediators was blocked by icatibant and dominant-negative Akt, indicating a kinin B2 receptor-Akt-mediated event. Similarly, kinin or transduction of kallikrein in cultured cardiomyocytes promoted cell viability and attenuated apoptosis induced by hypoxia/reoxygenation. The effect of kallikrein on cardiomyocyte survival was blocked by dominant-negative Akt and a constitutively active mutant of GSK-3␤, but it was facilitated by constitutively active Akt, catalytically inactive GSK-3␤, lithium, and caspase-3 inhibitor. Moreover, kallikrein promoted Bad⅐14-3-3 complex formation and inhibited Akt-GSK-3␤-dependent activation of caspase-3, whereas caspase-3 administration caused reduction of the Bad⅐14-3-3 complex, indicating an interaction between Akt-GSK-caspase-3 and Akt-Bad⅐14-3-3 signaling pathways. In conclusion, kallikrein/kinin protects against cardiomyocyte apoptosis in vivo and in vitro via Akt-Bad⅐14-3-3 and Akt-GSK-3␤-caspase-3 signaling pathways.

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Heat Shock Transcription Factor 1 Protects Cardiomyocytes From Ischemia/Reperfusion Injury

Cited by 67 publications

References 36 publications

C-phycocyanin protects against ischemia-reperfusion injury of heart through involvement of p38 MAPK and ERK signaling

C-phycocyanin protects against ischemia-reperfusion injury of heart through involvement of p38 MAPK and ERK signaling

Pharmacological induction of Hsp70 protects apoptosis-prone cells from doxorubicin: comparison with caspase-inhibitor- and cycle-arrest-mediated cytoprotection

Kallikrein/Kinin Protects against Myocardial Apoptosis after Ischemia/Reperfusion via Akt-Glycogen Synthase Kinase-3 and Akt-Bad·14-3-3 Signaling Pathways

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