Cardioprotective effect of KR-33889, a novel PARP inhibitor, against oxidative stress-induced apoptosis in H9c2 cells and isolated rat hearts

Dexmedetomidine (Dex) was reported to reduce oxidative stress and protect against myocardial Ischemia/Reperfusion (I/R) injury. However, the molecular mechanism involved in its antioxidant property is not fully elucidated. The present study was aimed at investigating whether the Trx1/Akt pathway participated in the cardioprotective effect of Dex. In the present study, I/R-induced myocardial injury in isolated rat hearts and OGD/R-induced injury in H9c2 cardiomyocytes were established. Our findings suggested that Dex ameliorated myocardial I/R injury by improving cardiac function, reducing myocardial apoptosis and oxidative stress, which was manifested by increased GSH and SOD contents, decreased ROS level, and MDA generation in both the isolated rat hearts and OGD/R-treated H9C2 cells. More importantly, it was found that the level of Trx1 was preserved, and Akt phosphorylation was significantly upregulated by Dex treatment. However, these effects of Dex were abolished by PX-12 (a specific Trx1 inhibitor) administration. Taken together, this study suggests that Dex plays a protective role in myocardial I/R injury, improves cardiac function, and relieves oxidative stress and cell apoptosis. Furthermore, our results present a novel signaling mechanism that the cardioprotective effect of Dex is at least partly achieved through the Trx1-dependent Akt pathway.

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Temperature preconditioning of isolated rat hearts - a potent cardioprotective mechanism involving a reduction in oxidative stress and inhibition of the mitochondrial permeability transition pore

The Journal of Physiology ◽

10.1113/jphysiol.2007.130369 ◽

2007 ◽

Vol 581 (3) ◽

pp. 1147-1161 ◽

Cited By ~ 68

Author(s):

Igor Khaliulin ◽

Samantha J. Clarke ◽

Hua Lin ◽

Joanna Parker ◽

M.-Saadeh Suleiman ◽

...

Keyword(s):

Oxidative Stress ◽

Mitochondrial Permeability Transition Pore ◽

Mitochondrial Permeability Transition ◽

Permeability Transition Pore ◽

Permeability Transition ◽

Mitochondrial Permeability ◽

Rat Hearts ◽

Isolated Rat

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The cardioprotective effect of dexmedetomidine on global ischaemia in isolated rat hearts

Resuscitation ◽

10.1016/j.resuscitation.2007.01.032 ◽

2007 ◽

Vol 74 (3) ◽

pp. 538-545 ◽

Cited By ~ 91

Author(s):

Hisako Okada ◽

Tadayoshi Kurita ◽

Toshiaki Mochizuki ◽

Koji Morita ◽

Shigehito Sato

Keyword(s):

Cardioprotective Effect ◽

Global Ischaemia ◽

Rat Hearts ◽

Isolated Rat

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Effect of Salidroside on Cardiac Functional Recovery

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.798-799.1030 ◽

2013 ◽

Vol 798-799 ◽

pp. 1030-1032

Author(s):

Yan Zhang ◽

Zhong Hua Zheng ◽

Yue Peng Wang ◽

Guo Liang Peng ◽

Liu Hang Wang

Keyword(s):

Flow Rate ◽

Functional Recovery ◽

Rat Heart ◽

Coronary Flow ◽

Left Ventricular ◽

Cardioprotective Effect ◽

Decrease Rate ◽

Rat Hearts ◽

Developed Pressure ◽

Isolated Rat

To investigate the cardioprotective effect of salidroside to rat heart subjected to 8-hour hypothermic storage and 2-hour normothermic reperfusion. Isolated rat hearts were perfused with Langendorff model; after 30 minutes of baseline, the hearts were arrested and stored by St. Thomas solution (STS) without (STS group) or with different concentration salidroside at 4 °C for 8 hours, then reperfused for 2 hours. Compared with STS group, both middle and high dosage in STS greatly improved the recovery of left ventricular developed pressure (LVDP), maximum LVDP increase and decrease rate (±dp/dt), coronary flow rate (CF). Our study demonstrated that the salidroside was beneficial to improving cardiac functional recovery.

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Cardioprotective effect of pindolol in ischemic-reperfused isolated rat hearts

European Journal of Pharmacology ◽

10.1016/0014-2999(92)90678-w ◽

1992 ◽

Vol 213 (2) ◽

pp. 171-181 ◽

Cited By ~ 4

Author(s):

Yoshihisa Nasa ◽

A.N. Ehsanul Hoque ◽

Kazuo Ichihara ◽

Yasushi Abiko

Keyword(s):

Cardioprotective Effect ◽

Rat Hearts ◽

Isolated Rat

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Hypaconitine protects H9c2 cells from oxidative stress-induced apoptosis

Journal of Medicinal Plants Research ◽

10.5897/jmpr11.1467 ◽

2012 ◽

Vol 6 (5) ◽

Author(s):

Zhi-Hui Li

Keyword(s):

Oxidative Stress ◽

H9c2 Cells ◽

Induced Apoptosis

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Role of calreticulin in the sensitivity of myocardiac H9c2 cells to oxidative stress caused by hydrogen peroxide

AJP Cell Physiology ◽

10.1152/ajpcell.00075.2005 ◽

2006 ◽

Vol 290 (1) ◽

pp. C208-C221 ◽

Cited By ~ 31

Author(s):

Yoshito Ihara ◽

Yoshishige Urata ◽

Shinji Goto ◽

Takahito Kondo

Keyword(s):

Oxidative Stress ◽

Hydrogen Peroxide ◽

Molecular Chaperone ◽

Vital Role ◽

H9c2 Cells ◽

Cardiac Physiology ◽

Caspase 12 ◽

A Cell ◽

Induced Apoptosis

Calreticulin (CRT), a Ca2+-binding molecular chaperone in the endoplasmic reticulum, plays a vital role in cardiac physiology and pathology. Oxidative stress is a main cause of myocardiac apoptosis in the ischemic heart, but the function of CRT under oxidative stress is not fully understood. In the present study, the effect of overexpression of CRT on susceptibility to apoptosis under oxidative stress was examined using myocardiac H9c2 cells transfected with the CRT gene. Under oxidative stress due to H2O2, the CRT-overexpressing cells were highly susceptible to apoptosis compared with controls. In the overexpressing cells, the levels of cytoplasmic free Ca2+ ([Ca2+]i) were significantly increased by H2O2, whereas in controls, only a slight increase was observed. The H2O2-induced apoptosis was enhanced by the increase in [Ca2+]i caused by thapsigargin in control cells but was suppressed by BAPTA-AM, a cell-permeable Ca2+ chelator in the CRT-overexpressing cells, indicating the importance of the level of [Ca2+]i in the sensitivity to H2O2-induced apoptosis. Suppression of CRT by the introduction of the antisense cDNA of CRT enhanced cytoprotection against oxidative stress compared with controls. Furthermore, we found that the levels of activity of calpain and caspase-12 were elevated through the regulation of [Ca2+]i in the CRT-overexpressing cells treated with H2O2 compared with controls. Thus we conclude that the level of CRT regulates the sensitivity to apoptosis under oxidative stress due to H2O2 through a change in Ca2+ homeostasis and the regulation of the Ca2+-calpain-caspase-12 pathway in myocardiac cells.

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