Effects of apoptosis-related proteins caspase-3, Bax and Bcl-2 on cerebral ischemia rats

Liu, Guangyi; Wang, Tao; Wang, Tinging; Jin-ming, Song; Zhou, Zhifeng

doi:10.3892/br.2013.153

Cited by 130 publications

(85 citation statements)

References 14 publications

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“…Moreover, the mRNA and protein expression levels of Caspase-3 and Bax could be reduced, whereas those of Bcl-2 could be increased after inhibition of the SOCS1-JAK2-STAT3 pathway. In conjunction with these studies, the activation of caspase-3 and Bax and the down-regulation of Bcl-2 have been reported to be strongly associated with neuron apoptosis, as Bax expression results in activated caspase-3 and indirectly inhibits Bcl-2 expression via the formation of Bax/Bcl-2 heterodimers, which initiate cell apoptosis following cerebral ischemia/reperfusion injury [28]. As an important signaling pathway, the JAK2/STAT3 pathway can regulate a variety of cell biological activities such as the immune response, cell differentiation and cell growth [29].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the SOCS1-JAK2-STAT3 Signaling Pathway Confers Neuroprotection in Rats with Ischemic Stroke

Wang

Qiao

Liu

et al. 2017

Cell Physiol Biochem

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Background: The present study aims to investigate the protective effects of the SOCS1-JAK2-STAT3 signaling pathway on neurons in a rat model of ischemic stroke. Methods: Our study was conducted using an ischemic stroke rat model. After the microglia were extracted, 40 neonatal Sprague-Dawley (SD) rats were assigned into the blank, AG490, model and negative control (NC) groups. The neurological function of all the rats was evaluated. Histopathological changes were observed. qRT-PCR and western blotting were applied to measure the expression of genes and proteins in the SOCS1-JAK2-STAT3 signaling pathway and related to apoptosis. The TUNEL assay was conducted to calculate the cellular morphology and apoptosis of neuronal cells. Cell viability was detected using the MTT assay. In addition, immunoassays were used to measure the content of superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) as well as the levels of oxidative stress. Results: Compared with the blank group, the model and NC groups showed higher neurological function scores—the cytoplasm of the neurons were cavitated, the organelles were reduced with unclear margins, some of the neurons were necrotic, and apoptosis was increased. In addition, the NC and model groups exhibited decreased cell viability, lower mRNA and protein expression of SOCS1 SOCS3 and bcl-2 and reduced SOD and GSH levels but higher mRNA and protein expression levels of AK2, STAT3,Bax and caspase-3 as well as increased protein expression of P-JAK2, P-STAT3 and activated caspase-3 (c-caspase-3). Moreover, the MDA levels were up-regulated in the NC and model groups. In contrast, opposing trends were found in the AG490 group compared with the NC and model groups. Conclusion: These data demonstrate that inhibiting the SOCS1-JAK2-STAT3 signaling pathway can reduce the loss of nerve function and apoptosis of neuronal cells, which provides a new target for the clinical treatment of ischemic stroke.

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Section: Discussionmentioning

confidence: 99%

Inhibition of the SOCS1-JAK2-STAT3 Signaling Pathway Confers Neuroprotection in Rats with Ischemic Stroke

Wang

Qiao

Liu

et al. 2017

Cell Physiol Biochem

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“…Bcl-2 has been shown to function as a negative regulator of cellular apoptosis (27) and increasing evidence has implicated Bcl-2 in the regulation of autophagy (28,29). Bcl-2 was found to bind to Beclin1 and disrupt autophagy, and overexpression of Bcl-2 in the heart inhibited autophagy in response to starvation.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of microRNA-101 attenuates hypoxia/reoxygenation-induced apoptosis through induction of autophagy in H9c2 cardiomyocytes

Jiang

Chen

et al. 2015

Molecular Medicine Reports

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Abstract. Autophagy is a cellular self-catabolic process responsible for the degradation of proteins and organelles. Autophagy is able to promote cell survival in response to stress, and increased autophagy amongst cardiomyocytes has been identified in conditions of heart failure, starvation and ischemia/reperfusion. However, the detailed regulatory mechanisms underlying autophagy in heart disease have remained elusive. MicroRNAs (miRNAs) have been implicated in the regulation of autophagy in cells under stress. In the present study, the protective effect of miRNA (miR)-101 on hypoxia/reoxygenation (H/R)-induced cardiomyocyte apoptosis was investigated. It was revealed that H/R induced apoptosis in H9c2 cardiomyocytes, accompanied by a downregulation of miR-101 expression. Further investigation identified Ras-related protein Rab-5A (RAB5A) as a direct target of miR-101. RAB5A was previously reported to be involved in autophagy; therefore, the present study further focused on the role of miR-101 in the regulation of autophagy under H/R and found that the inhibition of miR-101 attenuated H/R-induced apoptosis, at least partially, via the induction of autophagy. In conclusion, the results of the present study revealed a beneficial effect of miR-101 inhibition on H/R-induced apoptosis in cardiomyocytes, indicating that miR-101 inhibition may present a potential therapeutic agent in the treatment or prevention of heart diseases. IntroductionAutophagy is a cellular self-catabolic process responsible for the degradation of long-lived proteins and organelles. During autophagy, cytoplasmic constituents are sequestered into autophagosomes and degraded via the lysosomal pathway (1).Autophagy is able to promote cell survival in response to stress. However, progressive autophagy also induces cell death (2). Therefore, autophagy not only has a crucial role in the regulation of normal development, but dysregulated or defective autophagy is associated with disease.MicroRNAs (miRNAs) are a group of endogenous, non-coding, single-strand, small RNAs of 22-25 nucleotides, which regulate gene expression at the post-transcriptional level, predominantly through base pairing with the 3'-untranslated region (3'-UTR) of target mRNAs, which results in mRNA degradation or translational repression (3). It has been revealed that miRNAs regulate >30% of genes, which are associated with almost all major cellular processes, including cell proliferation, differentiation, apoptosis and migration, as well as immune responses (4). Myocardial tissue injury induced by ischemia and hypoxia is a major factor underlying the development of fatal diseases. The main cause of myocardial ischemic injury is myocardial cell apoptosis induced by myocardial hypoxia (5). Furthermore, subsequent reoxygenation may further aggravate the damage (6). Multiple miRNAs have been shown to function as protectors against hypoxia/reoxygenation (H/R)-induced myocardial injury (7-9). However, the specific molecular mechanisms underlying this effect have remained elusive.Accumu...

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“…Additionally, MDA expression increased and SOD expression decreased in the HIBD group. Studies have shown that neuronal apoptosis in an ischemia-reperfusion injury model may be associated with Bax upregulation and Bcl-2 downregulation [25]. Increased Bcl-2 expression and decreased Bax expression have been shown to be involved in the inhibition of HIBD in the subventricular zone of rats [26].…”

Section: Discussionmentioning

confidence: 99%

Effects of MicroRNA-592-5p on Hippocampal Neuron Injury Following Hypoxic-Ischemic Brain Damage in Neonatal Mice - Involvement of PGD2/DP and PTGDR

Sun

Guo

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: This study aimed to explore the effect of microRNA-592-5p (miR-592-5p) on hypoxic-ischemic brain damage (HIBD)-induced hippocampal neuronal injury in a neonatal mouse model relative to the involvement of one target gene, PTGDR, and the PGD2/ DP signaling pathway. Methods: A total of 30 neonatal mice aged 7 days were randomly selected to establish an HIBD mouse model. Hippocampal neuronal cells were transfected into a control group, a blank group, a negative control (NC) group, an miR-592-5p mimics group, an miR-592-5p inhibitors group, an siRNA-PTGDR group and an miR-592-5p inhibitors + siRNA-PTGDR group. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analyses were performed to detect the expression levels of miR-592-5p, PTGDR, DP2, Bcl-2 and Bax in tissues and cells. Cell proliferation, cell cycle and apoptosis were detected by MTT assay and flow cytometry, respectively. Results: The expression levels of miR-592-5p and Bcl-2 decreased, while the expression levels of PTGDR, DP2 and Bax increased in the HIBD group. PTGDR is a target gene of miR-592-2p. Compared with the NC and blank groups, the expression levels of PTGDR, DP2 and Bax decreased, while the expression levels of miR-592-5p and Bcl-2 increased in the miR-592-5p mimics group. The siRNA-PTGDR group showed the same trend as that observed in the miR-592-5p mimics group, except with no difference in miR-592-5p expression. The miR-592-5p inhibitors group showed an opposite gene expression trend compared to that in the miR-592-5p mimics group. The S phase of the cell cycle was prolonged, the G1 phase was reduced, proliferation was increased, and the apoptosis rate was decreased in the siRNA-PTGDR and miR-592-5p mimics groups. Opposite trends for cell cycle, proliferation and apoptosis were observed in the miR-592-5p inhibitors group. Conclusions: Our study suggests that miR-592-5p upregulation protects against hippocampal neuronal injury caused by HIBD by targeting PTGDR and inhibiting the PGD2/DP signaling pathway.

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Effects of apoptosis-related proteins caspase-3, Bax and Bcl-2 on cerebral ischemia rats

Cited by 130 publications

References 14 publications

Inhibition of the SOCS1-JAK2-STAT3 Signaling Pathway Confers Neuroprotection in Rats with Ischemic Stroke

Inhibition of the SOCS1-JAK2-STAT3 Signaling Pathway Confers Neuroprotection in Rats with Ischemic Stroke

Inhibition of microRNA-101 attenuates hypoxia/reoxygenation-induced apoptosis through induction of autophagy in H9c2 cardiomyocytes

Effects of MicroRNA-592-5p on Hippocampal Neuron Injury Following Hypoxic-Ischemic Brain Damage in Neonatal Mice - Involvement of PGD2/DP and PTGDR

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