ROS generated during early reperfusion contribute to intermittent hypobaric hypoxia-afforded cardioprotection against postischemia-induced Ca2+ overload and contractile dysfunction via the JAK2/STAT3 pathway

Wu, Lan; Tan, Jiliang; Wang, Zhihua; Chen, Yi-Xiong; Gao, Ling; Liu, Jinlong; Shi, Yulei; Endoh, Masao; Yang, Huang‐Tian

doi:10.1016/j.yjmcc.2015.02.015

Cited by 33 publications

(22 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…31, 53 In brief, the freshly isolated heart was successively perfused with nominally Ca 2+ -free Tyrode's solution containing collagenase II (240 U/ml, Worthington Biochemical) and protease (0.12 mg/ml, Sigma) for 18–22 min. Finally, the cell suspension from left ventricles was rinsed with Tyrode's solution followed by a gradual increase in the Ca 2+ concentration up to 1.25 mmol/l and 85% of isolated rod-shaped myocytes were Ca 2+ -tolerant.…”

Section: Methodsmentioning

confidence: 99%

Berbamine postconditioning protects the heart from ischemia/reperfusion injury through modulation of autophagy

Zheng

et al. 2017

Cell Death Dis

Self Cite

View full text Add to dashboard Cite

Pretreatment of berbamine protects the heart from ischemia/reperfusion (I/R) injury. However it is unknown whether it has cardioprotection when given at the onset of reperfusion (postconditioning (PoC)), a protocol with more clinical impact. Autophagy is upregulated in I/R myocardium and exacerbates cardiomyocyte death during reperfusion. However, it is unknown whether the autophagy during reperfusion is regulated by berbamine. Here we investigated whether berbamine PoC (BMPoC) protects the heart through regulation of autophagy by analyzing the effects of BMPoC on infarct size and/or cell death, functional recovery and autophagy in perfused rat hearts and isolated cardiomyocytes subjected to I/R. Berbamine from 10 to 100 nM given during the first 5 min of reperfusion concentration-dependently improved post-ischemic myocardial function and attenuated cell death. Similar protections were observed in cardiomyocytes subjected to simulated I/R. Meanwhile, BMPoC prevented I/R-induced impairment of autophagosome processing in cardiomyocytes, characterized by increased LC3-II level and GFP-LC3 puncta, and decreased p62 degradation. Besides, lysosomal inhibitor chloroquine did not induce additional increase of LC3-II and P62 abundance after I/R but it reversed the effects of BMPoC in those parameters in cardiomyocytes, suggesting that I/R-impaired autophagic flux is restored by BMPoC. Moreover, I/R injury was accompanied by enhanced expression of Beclin 1, which was significantly inhibited by BMPoC. In vitro and in vivo adenovirus-mediated knockdown of Beclin 1 in myocardium and cardiomyocytes restored I/R-impaired autophagosome processing, associated with an improvement of post-ischemic recovery of myocardial contractile function and a reduction of cell death, but it did not have additive effects to BMPoC. Conversely, overexpression of Beclin 1 abolished the cardioprotection of BMPoC as did by overexpression of an essential autophagy gene Atg5. Furthermore, BMPoC-mediated cardioprotection was abolished by a specific Akt1/2 inhibitor A6730. Our results demonstrate that BMPoC confers cardioprotection by modulating autophagy during reperfusion through the activation of PI3K/Akt signaling pathway.

show abstract

Section: Methodsmentioning

confidence: 99%

Berbamine postconditioning protects the heart from ischemia/reperfusion injury through modulation of autophagy

Zheng

et al. 2017

Cell Death Dis

Self Cite

View full text Add to dashboard Cite

show abstract

“…Additionally, STAT3 is introduced to involve in cardiac fibrosis of diabetes (28), while high glucose increased STAT3 activated by angiotensin II has been demonstrated to be produced mainly through a reactive oxygen species (ROS)-dependent mechanism (29). Recently, the ROS-activated STAT3 pathway has been characterized in early reperfusion of heart (30). High glucose is known as the main factor for inducing diabetes-associated cardiovascular dysfunctions.…”

Section: Phosphorylation Of Signal Transducer and Activator Of Transcmentioning

confidence: 99%

Phosphorylation of signal transducer and activator of transcription 3 induced by hyperglycemia is different with that induced by lipopolysaccharide or erythropoietin via receptor‑coupled signaling in cardiac cells

Chiu

Cheng

et al. 2017

Mol Med Report

View full text Add to dashboard Cite

The signal transducer and activator of transcription 3 (STAT3) is known to be involved in hypertrophy and fibrosis in cardiac dysfunction. The activation of STAT3 via the phosphorylation of STAT3 is required for the production of functional activity. It has been established that lipopolysaccharide (LPS)-induced phosphorylation of STAT3 in cardiomyocytes primarily occurs through a direct receptor-mediated action. This effect is demonstrated to be produced rapidly. STAT3 in cardiac fibrosis of diabetes is induced by high glucose through promotion of the STAT3-associated signaling pathway. However, the time schedule for STAT3 activation between LPS and high glucose appears to be different. Therefore, the difference in STAT3 activation between LPS and hyperglycemia in cardiomyocytes requires elucidation. The present study investigated the phosphorylation of STAT3 induced by LPS and hyperglycemia in the rat cardiac cell line H9c2. Additionally, phosphorylation of STAT3 induced by erythropoietin (EPO) via receptor activation was compared. Then, the downstream signals for fibrosis, including the connective tissue growth factor (CTGF) and matrix metalloproteinase (MMP)-9, were determined using western blotting, while the mRNA levels were quantified. LPS induced a rapid elevation of STAT3 phosphorylation in H9c2 cells within 30 min, similar to that produced by EPO. However, LPS or EPO failed to modify the mRNA level of STAT3, and/or the downstream signals for fibrosis. High glucose increased STAT3 phosphorylation to be stable after a long period of incubation. Glucose incubation for 24 h may augment the STAT3 expression in a dose-dependent manner. Consequently, fibrosis-associated signals, including CTGF and MMP-9 protein, were raised in parallel. In the presence of tiron, an antioxidant, these changes by hyperglycemia were markedly reduced, demonstrating the mediation of oxidative stress. Therefore, LPS-or EPO-induced STAT3 phosphorylation is different compared with that caused by high glucose in H9c2 cells. Sustained activation of STAT3 by hyperglycemia may promote the expression of fibrosis-associated signals, including CTGF and MMP-9, in H9c2 cells. Therefore, regarding the cardiac dysfunctions associated with diabetes and/or hyperglycemia, the identification of nuclear STAT3 may be more reliable compared with the assay of phosphorylated STAT3 in cardiac cells.

show abstract

“…It has been reported that SOCS3 shows a bipasic induction in response to pressure overload in the myocardium and is a key molecular switch for a negative feedback circuit involving both cardiomyocyte compensatory hypertrophy and survival. SOCS proteins are also upregulated after myocardial ischaemia but little is known about their role in remodeling [105]. STAT proteins are also regulated by the Protein Inhibitor of Activated STAT (PIAS) family of which seven members have been identified in mammals (PIAS 1, PIAS2, PIASx, PIASy) [79].…”

Section: Stat Activationmentioning

confidence: 99%

Understanding STAT3 signaling in cardiac ischemia

et al. 2016

View full text Add to dashboard Cite

Cardiovascular disease is the leading cause of death worldwide. It remains one of the greatest challenges to global health and will continue to dominate mortality trends in the future. Acute myocardial infarction results in 7.4 million deaths globally per annum. Current management strategies are centered on restoration of coronary blood flow via percutaneous coronary intervention, coronary artery bypass grafting and administration of anti-platelet agents. Such myocardial reperfusion accounts for 40-50 % of the final infarct size in most cases. Signaling transducer and activator of transcription 3 (STAT3) has been shown to have cardioprotective effects via canonical and non-canonical activation and modulation of mitochondrial and transcriptional responses. A significant body of in vitro and in vivo evidence suggests that activation of the STAT3 signal transduction pathway results in a cardio protective response to ischemia and attempts have been made to modulate this with therapeutic effect. Not only is STAT3 important for cardiomyocyte function, but it also modulates the cardiac microenvironment and communicates with cardiac fibroblasts. To this end, we here review the current evidence supporting the manipulation of STAT3 for therapeutic benefit in cardiac ischemia and identify areas for future research.

show abstract

ROS generated during early reperfusion contribute to intermittent hypobaric hypoxia-afforded cardioprotection against postischemia-induced Ca2+ overload and contractile dysfunction via the JAK2/STAT3 pathway

Cited by 33 publications

References 48 publications

Berbamine postconditioning protects the heart from ischemia/reperfusion injury through modulation of autophagy

Berbamine postconditioning protects the heart from ischemia/reperfusion injury through modulation of autophagy

Phosphorylation of signal transducer and activator of transcription 3 induced by hyperglycemia is different with that induced by lipopolysaccharide or erythropoietin via receptor‑coupled signaling in cardiac cells

Understanding STAT3 signaling in cardiac ischemia

Contact Info

Product

Resources

About