<i>Bcl6</i> knockdown aggravates hypoxia injury in cardiomyocytes via the P38 pathway

Gu, Yang; Luo, Man; Li, Yong; Su, Zhongping; Wang, Yaqing; Chen, Xiru; Zhang, Siqi; Sun, Wei; Kong, Xiangqing

doi:10.1002/cbin.11028

Cited by 19 publications

(21 citation statements)

References 29 publications

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“…These results indicate that BCL6 attenuates oxidative stress in Ang II-treated VSMCs and aortic media of SHR, which may be related to the downregulation of NOX4. The antioxidative effects of BCL6 in VSMCs were supported by previous findings that BCL6 overexpression inhibited oxidative stress response to etoposide and other chemotherapeutic reagents in B-cell lymphoma cells [18] and that BCL6 knockdown augmented the hypoxia-induced oxidative stress in cardiomyocytes [36]. The limitations in the present study were that the effect of specific inhibitor of NOX-2 or NOX-4 on DHE staining was not examined and that DHE staining was used to evaluate ROS production for in vivo experiments instead of a widely accepted marker of oxidative stress.…”

Section: Discussionsupporting

confidence: 53%

“…Accumulating evidences have shown that Ang II activates NOXs mediated by AT 1 R, which promotes ROS generation and subsequent VSMC proliferation [7–9]. BCL6 knockdown increased the transcription of NADPH oxidase subunits P67 and gp91 in normal cardiomyocytes, and hypoxia-induced P67 and gp91 upregulation in cardiomyocytes was enhanced by Bcl6 knockdown [36]. We found that Ang II-induced NAD(P)H oxidase activation, ROS generation, and NOX4 upregulation were attenuated by BCL6 overexpression but exacerbated by BCL6 knockdown in human VSMCs.…”

Section: Discussionmentioning

confidence: 99%

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BCL6 Attenuates Proliferation and Oxidative Stress of Vascular Smooth Muscle Cells in Hypertension

Chen

Zang

Qiu

et al. 2019

Oxidative Medicine and Cellular Longevity

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Proliferation and oxidative stress of vascular smooth muscle cells (VSMCs) contribute to vascular remodeling in hypertension and several major vascular diseases. B-cell lymphoma 6 (BCL6) functions as a transcriptional repressor. The present study is designed to determine the roles of BCL6 in VSMC proliferation and oxidative stress and underlying mechanism. Angiotensin (Ang) II was used to induce VSMC proliferation and oxidative stress in human VSMCs. Effects of BCL6 overexpression and knockdown were, respectively, investigated in Ang II-treated human VSMCs. Therapeutical effects of BCL6 overexpression on vascular remodeling, oxidative stress, and proliferation were determined in the aorta of spontaneously hypertensive rats (SHR). Ang II reduced BCL6 expression in human VSMCs. BCL6 overexpression attenuated while BCL6 knockdown enhanced the Ang II-induced upregulation of NADPH oxidase 4 (NOX4), production of reactive oxygen species (ROS), and proliferation of VSMCs. BCL6 expression was downregulated in SHR. BCL6 overexpression in SHR reduced NOX4 expression, ROS production, and proliferation of the aortic media of SHR. Moreover, BCL6 overexpression attenuated vascular remodeling and hypertension in SHR. However, BCL6 overexpression had no significant effects on NOX2 expression in human VSMCs or in SHR. We conclude that BCL6 attenuates proliferation and oxidative stress of VSMCs in hypertension.

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

BCL6 Attenuates Proliferation and Oxidative Stress of Vascular Smooth Muscle Cells in Hypertension

Chen

Zang

Qiu

et al. 2019

Oxidative Medicine and Cellular Longevity

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“…NRCMs were then isolated and moved to new plates and cultured with 1% bromodeoxyuridine for 48 h. To overexpress NGAL, cells were transfected with Ad-NGAL (Vigene Biosciences, Shangdong, China). Then, cells were exposed to hypoxia for 24 h. The hypoxia model was induced as described previously [12]. Cell were treated with constitutively-activated AKT adenovirus (Ad-ca.AKT) (Vigene Biosciences, Shangdong, China) to overexpress activated AKT.…”

Section: Methodsmentioning

confidence: 99%

“…TUNEL staining was performed as previously described [12]. Briefly, after cells were fixed and permeabilized, a TUNEL reaction mixture was used to label apoptotic cells.…”

Section: Methodsmentioning

confidence: 99%

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Neutrophil Gelatinase-Associated Lipocalin2 Exaggerates Cardiomyocyte Hypoxia Injury by Inhibiting Integrin β3 Signaling

Geng

et al. 2019

Med Sci Monit

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Background The neutrophil inflammatory protein, lipocalin-2 (NGAL), is elevated in certain forms of cardiac hypertrophy and acute heart failure. However, the specific role of NGAL in cardiac hypoxia injury is unclear. This study aimed to elucidate the functional role of NGAL in cardiomyocyte hypoxia injury. Material/Methods Neonatal rat cardiomyocytes were transfected with adenovirus [(Ad-NGAL] to overexpress human-NGAL and then were exposed to hypoxia for 24 h to establish a hypoxia model. Cell inflammation was detected by RT-PCT and ELISA assay. Cell apoptosis was detected by TUNEL assay. Oxidative stress was also detected by commercial kits. Results An increased inflammatory response, apoptosis, and augmented oxidative stress were observed after exposure to hypoxia, while NGAL overexpression in cells increased the expression and release of inflammatory cytokines. NGAL overexpression also increased the number of apoptotic cells and the imbalance of Bax/Bcl-2 protein expression. Moreover, NGAL overexpression increased the levels of reactive oxygen species and oxidase activity, but reduced anti-oxidase activity. Mechanistically, we found that NGAL decreased the expression of integrin β3, but not the expression of integrin avβ3 and avβ5, thus inhibiting the downstream protein AKT. When we used the constitutively activated AKT overexpression adenovirus to activate AKT, the deteriorated phenotype by NGAL was counteracted. Conclusions NGAL can directly affect cardiomyocytes and cause cardiomyocyte deteriorated hypoxia injury through inhibiting integrin β3 signaling.

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BCL‐6 promotes the methylation of miR‐34a by recruiting EZH2 and upregulating CTRP9 to protect ischemic myocardial injury

et al. 2021

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Acute myocardial infarction (AMI) and the following heart failure are public health problems faced all over the globe. The current study set out to investigate the role of B-cell lymphoma 6 (BCL-6) in cardiac protection after AMI.Initially, AMI mouse models and H9c2 cell oxygen-glucose deprivation (OGD) models were established. The cell models were transfected with the vectors containing oe-BCL-6, oe-EZH2, sh-EZH2, miR-34a mimic, and miR-34a inhibitor. RT-qPCR and Western blot analysis were applied to detect the expression patterns of microRNA-34a (miR-34a), BCL-6, enhancer of zeste homolog 2 (EZH2), and C1q tumor necrosis factor-related protein 9 (CTRP9) in the treated cell models. ChIP-qPCR and co-immunoprecipitation assay were performed to detect EZH2 enrichment and H3K27me3 levels in the miR-34a promoter region and the interaction between BCL-2 and EZH2, respectively. EdU staining, TUNEL staining, and flow cytometry were performed to detect cell proliferation and apoptosis, while ELISA was conducted to detect the oxidative stress levels. It was found that miR-34a was highly expressed in heart tissues of AMI models, while BCL-6 and EZH2 were poorly expressed. BCL-2 overexpression increased the recruitment of EZH2, upregulated H3K27me3 level in the miR-34a promoter region, and inhibited the miR-34a expression. Ctrp9, the downstream negative-regulatory molecule of miR-34a, was upregulated. Besides, miR-34a/CTRP9 expression changes were found to affect cardiomyocyte apoptosis, oxidation stress, and proliferation, and prevent myocardial injury in AMI mice. Our findings indicate that BCL-6 increases the level of H3K27me3 in the promoter region of miR-34a via EZH2 recruitment and CTRP9 upregulation, which inhibits the apoptosis of myocardial cells.

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Bcl6 knockdown aggravates hypoxia injury in cardiomyocytes via the P38 pathway

Cited by 19 publications

References 29 publications

BCL6 Attenuates Proliferation and Oxidative Stress of Vascular Smooth Muscle Cells in Hypertension

BCL6 Attenuates Proliferation and Oxidative Stress of Vascular Smooth Muscle Cells in Hypertension

Neutrophil Gelatinase-Associated Lipocalin2 Exaggerates Cardiomyocyte Hypoxia Injury by Inhibiting Integrin β3 Signaling

BCL‐6 promotes the methylation of miR‐34a by recruiting EZH2 and upregulating CTRP9 to protect ischemic myocardial injury

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