Cox-2 Negatively Affects the Protective Role of Propofol against Hypoxia/Reoxygenation Induced Cardiomyocytes Apoptosis through Suppressing Akt Signaling

Ma, Kangmu; Qiu, Jizheng; Zhou, Mi; Yang, Yang; Ye, Xiaofeng

doi:10.1155/2019/7587451

Cited by 4 publications

(3 citation statements)

References 41 publications

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“…A previous study reported that propofol exerted cardioprotection against myocardial I/R injury through the miR-451/HMGB1 axis in a H/R injury model of H9C2 cardiomyocytes ( 10 ). Another study reported that propofol exerted a protective effect on the H/R-challenged cardiomyocytes by activation of Akt phosphorylation ( 30 ). The present study confirmed that propofol was significantly beneficial to the survival and activity of cardiomyocytes subjected to H/R injury.…”

Section: Discussionmentioning

confidence: 99%

Propofol protects H9C2 cells against hypoxia/reoxygenation injury through miR‑449a and NR4A2

Qiu

Xie

2021

Exp Ther Med

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Propofol has been revealed to protect cardiomyocytes against myocardial ischemia injury, although the underlying mechanism remains incompletely understood. H9C2 cells were used to generate a hypoxia/reoxygenation (H/R) in vitro model for the present study. Reverse transcription-quantitative PCR and western blotting were performed to measure the expression levels of microRNA (miR)-449a and nuclear receptor subfamily 4 group A member 2 (NR4A2). The CCK-8, BrdU, EdU, and caspase-3 activity assays and western blot analysis were employed to detect cell viability, proliferation, and apoptosis. The target relationship between miR-449a and NR4A2 was verified through dual-luciferase reporter assays. The results confirmed that exposure of the cells to H/R resulted in severe cell injury. However, the presence of propofol improved cell activity by promoting cell viability and proliferation and inhibiting cell apoptosis. The beneficial effect of propofol on H/R-mediated injury could be abrogated by the inhibition of NR4A2 mediated by miR-449a. Thus, the present study demonstrated that propofol counteracted cardiomyocyte H/R injury by inhibiting miR-449a to upregulate NR4A2.

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Section: Discussionmentioning

confidence: 99%

Propofol protects H9C2 cells against hypoxia/reoxygenation injury through miR‑449a and NR4A2

Qiu

Xie

2021

Exp Ther Med

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“…Therefore, the present study established I/R-induced H9c2 cells to generate an in vitro myocardial ischemia-reperfusion injury model. The H9c2 cell line has the ability of cell division, and numerous studies have used H/R to induce H9c2 cells to establish myocardial ischemia injury model (12)(13)(14). In addition, due to the weak proliferative ability of primary cardiomyocytes (generally considered as telophase cells), the survival rate of primary cardiomyocytes is not high and the culture is difficult.…”

Section: Discussionmentioning

confidence: 99%

CPNE3 interaction with RACK1 protects against myocardial ischemia/reperfusion injury

2021

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Copine 3 (CPNE3) and receptor for activated C kinase 1 (RACK1) have been determined to be risk factors for patients with acute myocardial ischemia/reperfusion (I/R). The present study aimed to evaluate the role of CPNE3 and its interaction with RACK1 in myocardial (I/R) injury. Reverse transcription-quantitative PCR (RT-qPCR) and western blotting were performed to detect CPNE3 and RACK1 expression levels in H9c2 cells before and after the transfection of CPNE3 overexpression plasmid or small interfering RNA-RACK1. Cell viability was detected using a Cell Counting Kit-8 assay, and immunoprecipitation assays were performed to determine the interaction between CPNE3 and RACK1. A commercial kit was used to examine lactate dehydrogenase (LDH) levels. The expression levels of inflammatory cytokines were detected via RT-qPCR and western blotting. Cell apoptosis was assessed via TUNEL staining and western blotting. The results demonstrated that the expression levels of CPNE3 and RACK1 were decreased in hypoxia/reoxygenation (H/R)-induced H9c2 cardiomyocytes, which was consistent with the expression levels observed in the myocardial I/R injury rat model. It was found that CPNE3 overexpression upregulated RACK1 expression, increased cell viability and suppressed the release of LDH in H/R-induced H9c2 cells. Furthermore, CPNE3 overexpression inhibited the release of inflammatory cytokines and decreased cell apoptosis in H/R-induced cardiomyocytes by activating RACK1 expression. The present study suggested that CPNE3 served an important role in preventing I/R injury by interacting with RACK1, providing novel insight into the prevention of myocardial I/R injury, as well as the treatment and care of patients with myocardial I/R.

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“…In fact, beneficial effects of COX-2 in protection of the heart from ischemic injury have been reported also indicating that the use of COX inhibitors may have adverse effects in the setting of ischemia/reperfusion (I/R) [ 36 ]. In contrast, protective effects of COX-2 inhibition on CMs have also been reported [ 37 ]. The present study analyzes pathomechanisms of age-related idiopathic or DCM for which pathomechanisms are different from myocardial infarction or I/R injury as, for example, canonical STAT3 signaling is not or only moderately activated.…”

Section: Discussionmentioning

confidence: 99%

Increased prostaglandin-D2 in male STAT3-deficient hearts shifts cardiac progenitor cells from endothelial to white adipocyte differentiation

et al. 2020

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Cardiac levels of the signal transducer and activator of transcription factor-3 (STAT3) decline with age, and male but not female mice with a cardiomyocyte-specific STAT3 deficiency conditional knockout (CKO) display premature age-related heart failure associated with reduced cardiac capillary density. In the present study, isolated male and female CKO-cardiomyocytes exhibit increased prostaglandin (PG)-generating cyclooxygenase-2 (COX-2) expression. The PG-degrading hydroxyprostaglandin-dehydrogenase-15 (HPGD) expression is only reduced in male cardiomyocytes, which is associated with increased prostaglandin D2 (PGD2) secretion from isolated male but not female CKO-cardiomyocytes. Reduced HPGD expression in male cardiomyocytes derive from impaired androgen receptor (AR)–signaling due to loss of its cofactor STAT3. Elevated PGD2 secretion in males is associated with increased white adipocyte accumulation in aged male but not female hearts. Adipocyte differentiation is enhanced in isolated stem cell antigen-1 (SCA-1)+ cardiac progenitor cells (CPC) from young male CKO-mice compared with the adipocyte differentiation of male wild-type (WT)-CPC and CPC isolated from female mice. Epigenetic analysis in freshly isolated male CKO-CPC display hypermethylation in pro-angiogenic genes (Fgfr2, Epas1) and hypomethylation in the white adipocyte differentiation gene Zfp423 associated with up-regulated ZFP423 expression and a shift from endothelial to white adipocyte differentiation compared with WT-CPC. The expression of the histone-methyltransferase EZH2 is reduced in male CKO-CPC compared with male WT-CPC, whereas no differences in the EZH2 expression in female CPC were observed. Clonally expanded CPC can differentiate into endothelial cells or into adipocytes depending on the differentiation conditions. ZFP423 overexpression is sufficient to induce white adipocyte differentiation of clonal CPC. In isolated WT-CPC, PGD2 stimulation reduces the expression of EZH2, thereby up-regulating ZFP423 expression and promoting white adipocyte differentiation. The treatment of young male CKO mice with the COX inhibitor Ibuprofen or the PGD2 receptor (DP)2 receptor antagonist BAY-u 3405 in vivo increased EZH2 expression and reduced ZFP423 expression and adipocyte differentiation in CKO-CPC. Thus, cardiomyocyte STAT3 deficiency leads to age-related and sex-specific cardiac remodeling and failure in part due to sex-specific alterations in PGD2 secretion and subsequent epigenetic impairment of the differentiation potential of CPC. Causally involved is the impaired AR signaling in absence of STAT3, which reduces the expression of the PG-degrading enzyme HPGD.

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Cox-2 Negatively Affects the Protective Role of Propofol against Hypoxia/Reoxygenation Induced Cardiomyocytes Apoptosis through Suppressing Akt Signaling

Cited by 4 publications

References 41 publications

Propofol protects H9C2 cells against hypoxia/reoxygenation injury through miR‑449a and NR4A2

Propofol protects H9C2 cells against hypoxia/reoxygenation injury through miR‑449a and NR4A2

CPNE3 interaction with RACK1 protects against myocardial ischemia/reperfusion injury

Increased prostaglandin-D2 in male STAT3-deficient hearts shifts cardiac progenitor cells from endothelial to white adipocyte differentiation

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