Amifostine Pretreatment Attenuates Myocardial Ischemia/Reperfusion Injury by Inhibiting Apoptosis and Oxidative Stress

Wu, Shaoze; Tao, Luyuan; Wang, Jiaoni; Xu, Zhiqiang; Wang, Jie; Xue, Yan; Huang, Kaiyu; Lin, Jiafeng; Li, Lei; Ji, Kangting

doi:10.1155/2017/4130824

Cited by 31 publications

(24 citation statements)

References 31 publications

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“…In the current study, we found activation of ROS and MAPKs signaling in heart of I/R mice, suggesting the involvement of ROS and MAPKs in cardiac I/R injury. Indeed, our in vivo and in vitro data showed that both ROS and MAPKs mediated I/R- and A/R-induced cardiomyocyte apoptosis, because pharmacological inhibition of ROS or MAPKs almost completely abolished the increase in apoptotic cell population, in line with the important roles of ROS and MAPKs in regulating apoptotic heart cell death [23, 24, 35]. Since ROS and MAPKs seem to be involved in the same signaling pathway, we proceeded to test the sequence of ROS and MAPKs.…”

Section: Discussionmentioning

confidence: 81%

“…Since both ROS and MAPKs have been considered important mediators of cell apoptosis [23-25], we initially investigated the effect I/R injury on these pathways activation in cardiomyocytes. H 2 DCF-DA staining showed that the ROS production in heart slices from I/R mice was dramatically increased as compared with sham mice (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The imbalance between the production and scavenging of ROS can cause an irreversible damage to cells, eventually leading to cell apoptosis [22]. Antioxidant agents have been considered as a potent therapeutic approach for the treatment of I/R injury [23]. MAPKs, including p38, JNK and Erks, are linked to ROS production, which has a pivotal role in cardiovascular diseases.…”

Section: Discussionmentioning

confidence: 99%

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Overexpression of TIMP3 Protects Against Cardiac Ischemia/Reperfusion Injury by Inhibiting Myocardial Apoptosis Through ROS/Mapks Pathway

Liu¹,

Jing

Dong³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Myocardial ischemia/reperfusion (I/R) injury remains a great challenge in clinical therapy. Tissue inhibitor of metalloproteinases 3 (TIMP3) plays a crucial role in heart physiological and pathophysiological processes. However, the effects of TIMP3 on I/R injury remain unknown. Methods: C57BL/6 mice were infected with TIMP3 adenovirus by local delivery in myocardium followed by I/R operation or doxorubicin treatment. Neonatal rat cardiomyocytes were pretreated with TIMP3 adenovirus prior to anoxia/reoxygenation (A/R) treatment in vitro. Histology, echocardiography, in vivo phenotypical analysis, flow cytometry and western blotting were used to investigate the altered cardiac function and underlying mechanisms. Results: The results showed that upregulation of TIMP3 in myocardium markedly inhibited myocardial infarct areas and the cardiac dysfunction induced by I/R or by doxorubicin treatment. TUNEL staining revealed that TIMP3 overexpression attenuated I/R-induced myocardial apoptosis, accompanied by decreased Bax/Bcl-2 ratio, Cleaved Caspase-3 and Cleaved Caspase-9 expression. In vitro, A/R-induced cardiomyocyte apoptosis was abrogated by pharmacological inhibition of reactive oxygen species (ROS) production or MAPKs signaling. Attenuation of ROS production reversed A/R-induced MAPKs activation, whereas MAPKs inhibitors showed on effect on ROS production. Furthermore, in vivo or in vitro overexpression of TIMP3 significantly inhibited I/R- or A/R-induced ROS production and MAPKs activation. Conclusion: Our findings demonstrate that TIMP3 upregulation protects against cardiac I/R injury through inhibiting myocardial apoptosis. The mechanism may be related to inhibition of ROS-initiated MAPKs pathway. This study suggests that TIMP3 may be a potential therapeutic target for the treatment of I/R injury.

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Section: Discussionmentioning

confidence: 81%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Overexpression of TIMP3 Protects Against Cardiac Ischemia/Reperfusion Injury by Inhibiting Myocardial Apoptosis Through ROS/Mapks Pathway

Liu¹,

Jing

Dong³

et al. 2017

Cell Physiol Biochem

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“…Myocardial I/R injury is a complex pathophysiological process associated with a variety of mechanisms, including oxidative stress, cell apoptosis and inflammatory responses (5)(6)(7). The particular mechanisms underlying the development of myocardial I/R injury are unclear; however, it has been reported that excessive production of reactive oxygen species (ROS) is a primary factor that activates a variety of molecular cascades of apoptosis, thereby aggravating myocardial I/R injury (8,9). Therefore, inhibition of ROS production or the scavenging of free radicals may be potential therapeutic strategy to attenuate I/R injury.…”

Section: Introductionmentioning

confidence: 99%

Melatonin protects H9c2 cells against ischemia/reperfusion‑induced apoptosis and oxidative stress via activation of the Nrf2 signaling pathway

et al. 2018

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Melatonin can protect against cardiac ischemia/reperfusion (I/R) injury in models in vitro and in vivo by regulating oxidative stress and apoptosis; however, the precise molecular mechanisms involved remain unclear. Nuclear factor erythroid 2‑related factor 2 (Nrf2) is a transcription factor, which has been associated with the regulation of oxidative stress by translocating to the nucleus. Therefore, the present study investigated whether activation of the Nrf2 signaling pathway may be responsible for the protective effects of melatonin on I/R‑injured cardiomyocytes. In the present study, H9c2 cells were subjected to simulated I/R (SIR) injury and pretreated with melatonin and/or Nrf2 small interfering RNA (siRNA). Cell viability was detected via Cell Counting kit‑8 assay, apoptosis was examined by caspase‑3 cleavage and activity analysis; oxidative stress levels were determined by specific activity analysis assays. In the present study, it was observed that SIR induced significant increases in apoptosis and oxidative stress, and enhanced Nrf2 expression within H9c2 cells. Pretreatment with melatonin partially reversed these alterations and promoted Nrf2 nuclear translocation. Transfection with Nrf2 siRNA inhibited the protective effects of melatonin on SIR‑induced H9c2 cells. These results indicated that melatonin may protect H9c2 cells against I/R injury by reducing apoptosis and oxidative stress; this effect may be mediated via activation of the Nrf2 signaling pathway. Collectively, the results of the present study may suggest melatonin as a potential therapeutic agent against cardiac I/R injury.

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“…7) Therefore, antioxidant agents have been proposed to treat myocardial ischemia reperfusion. 8) Hydrogen peroxide (H2O2), as an exogenous ROS, could activate caspase-3 and subsequently activates the mitochondria-dependent pathway. 9) However, it is not clear whether H2O2 affects the expression of miR-208a.…”

mentioning

confidence: 99%

MicroRNA-208a Correlates Apoptosis and Oxidative Stress Induced by H<sub>2</sub>O<sub>2</sub> through Protein Tyrosine Kinase/Phosphatase Balance in Cardiomyocytes

Liu

Sun

2018

Int. Heart J.

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MicroRNAs, a class of small and non-encoding RNAs that transcriptionally or post-transcriptionally modulate the expression of their target genes, have been implicated as critical regulatory molecules in ischemia-/reperfusion-induced cardiac injury. In the present study, we report on the role of miR-208a in myocardial I/R injury and the underlying cardio-protective mechanism. The gain-of-function and loss-of-function were used to explore the effects of miR-208a on cardiac injury induced by HO in cardiomyocytes. As predicted, knockdown of endogenous miR-208a significantly decreased the level of cellular reactive oxygen species (ROS) and reduced cardiomyocyte apoptosis. In addition, miR-208a overexpression increased the ROS level and attenuated cell apoptosis in cardiomyocytes. Furthermore, protein tyrosine phosphatase receptor type G (PTPRG) and protein tyrosine phosphatase, non-receptor type 4 (PTPN4), which participate in regulating the level of cellular protein tyrosine phosphorylation balance, were predicted and verified as potential miR-208a targets using bioinformatics and luciferase assay. In summary, this study demonstrated that miR-208a plays a critical protective role in ROS-induced cardiac apoptosis.

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Amifostine Pretreatment Attenuates Myocardial Ischemia/Reperfusion Injury by Inhibiting Apoptosis and Oxidative Stress

Cited by 31 publications

References 31 publications

Overexpression of TIMP3 Protects Against Cardiac Ischemia/Reperfusion Injury by Inhibiting Myocardial Apoptosis Through ROS/Mapks Pathway

Overexpression of TIMP3 Protects Against Cardiac Ischemia/Reperfusion Injury by Inhibiting Myocardial Apoptosis Through ROS/Mapks Pathway

Melatonin protects H9c2 cells against ischemia/reperfusion‑induced apoptosis and oxidative stress via activation of the Nrf2 signaling pathway

MicroRNA-208a Correlates Apoptosis and Oxidative Stress Induced by H<sub>2</sub>O<sub>2</sub> through Protein Tyrosine Kinase/Phosphatase Balance in Cardiomyocytes

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