Ginsenoside RK3 Prevents Hypoxia-Reoxygenation Induced Apoptosis in H9c2 Cardiomyocytes via AKT and MAPK Pathway

Sun, Jing; Sun, Guibo; Meng, Xiangbao; Wang, Hongwei; Wei, Min; Qin, Meng; Ma, Bo; Luo, Yun; Yu, Yingli; Chen, Rongchang; Ai, Qidi; Sun, Xiaobo

doi:10.1155/2013/690190

Cited by 47 publications

(42 citation statements)

References 36 publications

(32 reference statements)

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“…Cardiomyocyte apoptosis is strongly associated with the pathogenesis of hypoxia and I/R injury [16]. To date, increasing studies suggest that ER stress plays a crucial role in I/R-induced cardiomyocyte apoptosis [19].…”

Section: Discussionmentioning

confidence: 99%

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Elatoside C protects against hypoxia/reoxygenation-induced apoptosis in H9c2 cardiomyocytes through the reduction of endoplasmic reticulum stress partially depending on STAT3 activation

Wang

Meng

et al. 2014

Apoptosis

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Endoplasmic reticulum (ER) stress-induced apoptosis has been suggested to contribute to myocardial ischemia-reperfusion (I/R) injury. Elatoside C is one of the major triterpenoid compounds isolated from Aralia elata that is known to be cardioprotective. However, its effects on I/R injury to cardiac myocytes have not been clarified. This study aimed to investigate the possible protective effect of Elatoside C against hypoxia/reoxygenation (H/R)-induced H9c2 cardiomyocyte injury and its underlying mechanisms. H9c2 cardiomyocytes were subjected to H/R in the presence of Elatoside C. Our results showed that Elatoside C (25 μM) treatment provided significant protection against H/R-induced cell death, as evidenced by improved cell viability, maintained mitochondrial membrane potential, diminished mitochondrial ROS, and reduced apoptotic cardiomyocytes (P < 0.05). These changes were associated with the inhibition of ER stress-associated apoptosis markers (GRP78, CHOP, Caspase-12 and JNK), as well as the increased phosphorylation of STAT3 and an increased Bcl2/Bax ratio. Moreover, these effects of Elatoside C were prevented by the STAT3 inhibitor Stattic. Taken together, these results suggested that Elatoside C can alleviate H/R-induced cardiomyocyte apoptosis most likely by activating the STAT3 pathways and reducing ER stress-associated apoptosis.

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Section: Discussionmentioning

confidence: 99%

“…The cells were maintained at 37°C with 100 % relative humidity in a CO 2 incubator containing 5 % CO 2 at 37°C. The H/R procedures were modified from a previous study [16]. High glucose DMEM medium was changed to DMEM with no glucose to mimic ischemia.…”

Section: Cell Culture and Hypoxia/reoxygenationmentioning

confidence: 99%

Elatoside C protects against hypoxia/reoxygenation-induced apoptosis in H9c2 cardiomyocytes through the reduction of endoplasmic reticulum stress partially depending on STAT3 activation

Wang

Meng

et al. 2014

Apoptosis

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“…Ischemic heart disease is a complicated heart disorder that is a common cause of death in the world, most commonly caused by atherosclerosis or occlusion [3,6]. Ischemia and ischemia coupled with reperfusion has been shown induce programmed cell death [7].…”

Section: Introductionmentioning

confidence: 99%

The structure-activity relationship of ginsenosides on hypoxia-reoxygenation induced apoptosis of cardiomyocytes

Feng

Liu

Wang

et al. 2017

Biochemical and Biophysical Research Communications

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Ginsenosides have been studied extensively in recent years due to their therapeutic effects in cardiovascular diseases. While most studies examined the different ginsenosides individually, few studies compare the therapeutic effects among the different types. This study examined how effective protopanaxadiol, protopanaxatriol ginsenosides Rh2, Rg3, Rh1, and Rg2 of the ginsenoside family are in protecting H9c2 cardiomyocytes from damage caused by hypoxia/reoxygenation. In the current study, a model of myocardial ischemia and reperfusion was induced in H9c2 cardiomyocytes by oxygen deprivation via a hypoxia chamber followed by reoxygenation. Our data show that structures similar to that of protopanaxadiol, which lacked the hydroxide group at C6, were more effective in lowering apoptosis than structures similar to protopanaxatriol with a hydroxide group at C6. As the compounds increased in size and complexity, the cardioprotective effects diminished. In addition, the S enantiomer proved to be more effective in cardioprotection than the R enantiomer. Furthermore, the immunoblotting analysis demonstrated that ginsenosides activate AMPK but suppress JNK signaling pathways during hypoxia/reoxygenation. Thus, ginsenosides treatment attenuated hypoxia/reoxygenation-induced apoptosis via modulating cardioprotective AMPK and inflammation-related JNK signaling pathways.

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“…Ischemic heart disease is a major cause of morbidity and mortality throughout the world (Sun et al 2013a, b). Hundreds of experimental interventions have been reported to protect the ischemic myocardium in experimental animals.…”

Section: Introductionmentioning

confidence: 99%

“…Studies about myocardial I/R injury show that the major mechanism causing cellular death is apoptosis, which occurs during the early phase of myocardial ischemia (Sun et al 2013a, b). Apoptosis is characterized by increased expression of pro-apoptotic proteins and activation of caspases (Abbate et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Nucleostemin exerts anti-apoptotic function via p53 signaling pathway in cardiomyocytes

Zhang

Shi

Qian

et al. 2015

In Vitro Cell.Dev.Biol.-Animal

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Cardiomyocytes apoptosis following reperfusion injury causes irreversible damage to cardiac function. Understanding the mechanisms underlying cardiomyocytes death under these conditions can be helpful to identify strategies to abrogate such detrimental effects. Stem cell-specific proteins and regulatory pathways become important in understanding reparative processes in the myocardium. One such regulatory protein named nucleostemin (NS) has vital roles in cardiac ischemia. Although the relationship between NS and cell apoptosis has been studied, it is unknown how NS is controlled and how it participates in cardiomyocytes apoptosis induced by ischemia reperfusion (I/R). In the present study, we aimed to investigate the direct role of NS in myocardial I/R. In vivo, NS was highly expressed in cardiac tissues after I/R. Double immunofluorescent staining showed that NS located in the nucleolar of cardiomyocytes and correlated with cardiomyocytes apoptosis. Furthermore, in vitro primary rat cardiomyocytes increased NS expression induced by hypoxia-reoxygenation (H/R) treatment, in line with results in vivo. Suppression of NS expression by siNS promoted the expression of terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL)-positive cells p53 and cleaved caspase-3, which demonstrates I/R may require increased expression of NS to suppress p53 activation and maintain cardiomyocytes survival.

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Ginsenoside RK3 Prevents Hypoxia-Reoxygenation Induced Apoptosis in H9c2 Cardiomyocytes via AKT and MAPK Pathway

Cited by 47 publications

References 36 publications

Elatoside C protects against hypoxia/reoxygenation-induced apoptosis in H9c2 cardiomyocytes through the reduction of endoplasmic reticulum stress partially depending on STAT3 activation

Elatoside C protects against hypoxia/reoxygenation-induced apoptosis in H9c2 cardiomyocytes through the reduction of endoplasmic reticulum stress partially depending on STAT3 activation

The structure-activity relationship of ginsenosides on hypoxia-reoxygenation induced apoptosis of cardiomyocytes

Nucleostemin exerts anti-apoptotic function via p53 signaling pathway in cardiomyocytes

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