Assessment of global ischemic/reperfusion and Tacrolimus administration on CA1 region of hippocampus: gene expression profiles of BAX and BCL2 genes

Badr, Ramak; Hashemi, Mehrdad; Javadi, Gholamreza; Movafagh, Abolfazl; Mahdian, Reza

doi:10.4149/bll_2016_071

Cited by 13 publications

(9 citation statements)

References 15 publications

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“…Therefore, the balance between apoptotic Bax proteins and anti-apoptotic Bcl-2 proteins determines activation and inhibition of the intrinsic apoptosis pathway. Consistent with the results of this study, previous studies that used different experimental models have reported tacrolimus-induced apoptosis was associated with a decrease in Bcl-2/Bax ratio and/or caspase-3 activation [16,35,43,44,45,46]. Moreover, several natural products with antioxidant properties have been shown to protect against tacrolimus-mediated cytotoxicity and tacrolimus-induced suppressions of Bcl-2/Bax ratio and/or caspase-3 activation [16,34,43,44], which are very similar to the results of this study.…”

Section: Discussionsupporting

confidence: 92%

Protective Effects of Nargenicin A1 against Tacrolimus-Induced Oxidative Stress in Hirame Natural Embryo Cells

Park

Kwon

Hwang

et al. 2019

IJERPH

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Tacrolimus is widely used as an immunosuppressant to reduce the risk of rejection after organ transplantation, but its cytotoxicity is problematic. Nargenicin A1 is an antibiotic extracted from Nocardia argentinensis and is known to have antioxidant activity, though its mode of action is unknown. The present study was undertaken to evaluate the protective effects of nargenicin A1 on DNA damage and apoptosis induced by tacrolimus in hirame natural embryo (HINAE) cells. We found that reduced HINAE cell survival by tacrolimus was due to the induction of DNA damage and apoptosis, both of which were prevented by co-treating nargenicin A1 or N-acetyl-l-cysteine, a reactive oxygen species (ROS) scavenger, with tacrolimus. In addition, apoptosis induction by tacrolimus was accompanied by increases in ROS generation and decreases in adenosine triphosphate (ATP) levels caused by mitochondrial dysfunction, and these changes were significantly attenuated in the presence of nargenicin A1, which further indicated tacrolimus-induced apoptosis involved an oxidative stress-associated mechanism. Furthermore, nargenicin A1 suppressed tacrolimus-induced B-cell lymphoma-2 (Bcl-2) down-regulation, Bax up-regulation, and caspase-3 activation. Collectively, these results demonstrate that nargenicin A1 protects HINAE cells against tacrolimus-induced DNA damage and apoptosis, at least in part, by scavenging ROS and thus suppressing the mitochondrial-dependent apoptotic pathway.

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Section: Discussionsupporting

confidence: 92%

Protective Effects of Nargenicin A1 against Tacrolimus-Induced Oxidative Stress in Hirame Natural Embryo Cells

Park

Kwon

Hwang

et al. 2019

IJERPH

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“…The Bcl-2 family members (Bcl-2, Bcl-xL, Bax, Bak) are involved in the regulation of apoptotic signaling by mediating mitochondrial membrane permeability. Bcl-2 plays a vital role in the anti-apoptosis process by inhibiting Bax migration to the mitochondrial membrane or interfering with the Bak oligomerization process (26). The present results demonstrated that PAR2 deficiency attenuated cardiomyocyte apoptosis after H/R with decreased c-PARP and increased Bcl-2 expression levels.…”

Section: Discussionmentioning

confidence: 99%

Proteinase‑activated receptor�2 deficiency is a protective factor against cardiomyocyte apoptosis during myocardial ischemia/reperfusion injury

Wang

Zhang

et al. 2019

Mol Med Report

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Previous studies have established that proteinase- activated receptor 2 (PAR2) activation protects against myocardial ischemia/reperfusion injury (MI/RI). However, the role of PAR2 deficiency in MI/RI remains unclear. The aim of the present study was to examine the effect of PAR2 deficiency on cardiomyocyte apoptosis and to clarify the potential molecular mechanisms for its protective effect against MI/RI. Using a mouse model of MI/RI, cardiac function was evaluated by echocardiography, infarct size was assessed by triphenyltetrazolium chloride staining, and myocardial cell apoptosis was measured by terminal deoxynucleotide transferase-mediated dUTP nick end-labeling staining. Annexin V/propidium iodide staining, and expression of Bcl-2 and cleaved PARP were determined to assess apoptosis in myocardial H9c2 cells exposed to hypoxia/reoxygenation (H/R) injury-simulating MI/RI. Phosphorylated ERK1/2, JNK, and p38 MAPK protein expression levels were analyzed by western blotting. The findings indicated that PAR2 deficiency markedly reduced cardiomyocyte apoptosis in the MI/RI mouse model, as well as in myocardial H9c2 cells exposed to H/R. Furthermore, PAR2 knockdown clearly prevented phosphorylation of ERK1/2 and JNK in myocardial H9c2 cells. The results revealed that PAR2 deficiency alleviated MI/RI-associated apoptosis by inhibiting phosphorylation of ERK1/2 and JNK. Therefore, targeted PAR2 silencing may be a potential therapeutic approach for alleviation of MI/RI.

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“…Previous studies have demonstrated that tacrolimus alleviates I/R injury in various organs, including the ovary, liver and brain (16,17). It has also been revealed that tacrolimus may exert anti-oxidative and anti-apoptotic Association of the PPARγ/PI3K/Akt pathway with the cardioprotective effects of tacrolimus in myocardial ischemic/reperfusion injury effects (18,19). However, the effects of tacrolimus on MIRI and the exact mechanism are yet to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Association of the PPARγ/PI3K/Akt pathway with the cardioprotective effects of tacrolimus in myocardial ischemic/reperfusion injury

Bilali

Qiao

et al. 2018

Mol Med Report

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Myocardial ischemia/reperfusion injury (MIRI) induces severe arrhythmias and has a high risk of mortality. The aim of the present study was to investigate the effect of tacrolimus on arrhythmias, cardiac function, oxidative stress and myocardium apoptosis induced by MIRI, and to elucidate the underlying mechanism. The effects of MIRI and tacrolimus on arrhythmias, cardiac function parameters, myocardial oxidative stress and apoptosis were investigated in a rat model of MIRI. The phosphorylation of peroxisome proliferator‑activated receptor γ (PPARγ) and protein kinase B (Akt) was investigated via western blotting. After rats were treated with inhibitors of PPARγ/phosphoinositide 3‑kinase (PI3K)/Akt, cardiac function parameters were measured. The results demonstrated that the MIRI procedure induced arrhythmias and significant impairment of cardiac function, oxidative stress and apoptosis in cardiomyocytes (P<0.05). Tacrolimus significantly alleviated the arrhythmias and impairment of cardiac function and inhibited the oxidative stress and apoptosis in cardiomyocytes (P<0.05). The phosphorylation of PPARγ and Akt was significantly activated by tacrolimus, whereas inhibitors of PPARγ/PI3K/Akt significantly abolished the effects of tacrolimus (P<0.05). Together, these results suggest that tacrolimus may protect rats from MIRI through activation of the PPARγ/PI3K/Akt pathway.

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Assessment of global ischemic/reperfusion and Tacrolimus administration on CA1 region of hippocampus: gene expression profiles of BAX and BCL2 genes

Cited by 13 publications

References 15 publications

Protective Effects of Nargenicin A1 against Tacrolimus-Induced Oxidative Stress in Hirame Natural Embryo Cells

Protective Effects of Nargenicin A1 against Tacrolimus-Induced Oxidative Stress in Hirame Natural Embryo Cells

Proteinase‑activated receptor�2 deficiency is a protective factor against cardiomyocyte apoptosis during myocardial ischemia/reperfusion injury

Association of the PPARγ/PI3K/Akt pathway with the cardioprotective effects of tacrolimus in myocardial ischemic/reperfusion injury

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