Impact of UCP2 depletion on heat stroke-induced mitochondrial function in human umbilical vein endothelial cells

Huang, Wei; Mao, Liangfeng; Xie, Weidang; Cai, Sumin; Huang, Qiaobing; Liu, Yanan; Chen, Zhongqing

doi:10.1080/02656736.2022.2032846

Cited by 9 publications

(6 citation statements)

References 44 publications

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“…dePs, differentially expressed proteins; KO, knockout; HS, heat stroke; CON, control; HUVECs, human umbilical vein endothelial cells; No sig, not significant; KEGG, Kyoto encyclopedia of Genes and Genomes; Go, Gene ontology. be damaged by HS a high temperature of 43˚C (29)(30)(31). To identify the specific gene associated with thermal tolerance, genome-wide criSPr-cas9 screen research was conducted on HuVecs (10).…”

Section: Discussionmentioning

confidence: 99%

DNAJA1‑knockout alleviates heat stroke‑induced endothelial barrier disruption via improving thermal tolerance and suppressing the MLCK‑MLC signaling pathway

Li,

Wang,

Chang

et al. 2024

Mol Med Rep

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endothelial barrier disruption plays a key role in the pathophysiology of heat stroke (HS). Knockout of dnaJa1 (dnaJa1-Ko) is thought to be protective against HS based on a genome-wide criSPr-cas9 screen experiment. The present study aimed to illustrate the function of dnaJa1-Ko against HS in human umbilical vein endothelial cells. dnaJa1-Ko cells were infected using a lentivirus to investigate the role of dnaJa1-Ko in HS-induced endothelial barrier disruption. it was shown that dnaJa1-Ko could ameliorate decreased cell viability and increased cell injury, according to the results of cell counting Kit-8 and lactate dehydrogenase assays. Moreover, HS-induced endothelial cell apoptosis was inhibited by dnaJa1-Ko, as indicated by annexin V-FiTc/Pi staining and cleaved-caspase-3 expression using flow cytometry and western blotting, respectively. Furthermore, the endothelial barrier function, as measured by transepithelial electrical resistance and FiTc-dextran, was sustained during HS. DNAJA1-KO was not found to have a significant effect on the expression and distribution of cell junction proteins under normal conditions without HS. However, dnaJa1-Ko could effectively protect the HS-induced decrease in the expression and distribution of cell junction proteins, including zonula occludens-1, claudin-5, junctional adhesion molecule a and occludin. A total of 4,394 proteins were identified using proteomic analysis, of which 102 differentially expressed proteins (dePs) were activated in HS-induced wild-type cells and inhibited by dnaJa1-Ko. dePs were investigated by enrichment analysis, which demonstrated significant enrichment in the 'calcium signaling pathway' and associations with vascular-barrier regulation. Furthermore, the 'myosin light-chain kinase (MlcK)-Mlc signaling pathway' was proven to be activated by HS and inhibited by dnaJa1-Ko, as expected. Moreover, dnaJa1-Ko mice and a HS mouse model were established to demonstrate the protective effects on endothelial barrier in vivo. in conclusion, the results of the present study suggested that dnaJa1-Ko alleviates HS-induced endothelial barrier disruption by improving thermal tolerance and suppressing the MlcK-Mlc signaling pathway.

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Section: Discussionmentioning

confidence: 99%

DNAJA1‑knockout alleviates heat stroke‑induced endothelial barrier disruption via improving thermal tolerance and suppressing the MLCK‑MLC signaling pathway

Li,

Wang,

Chang

et al. 2024

Mol Med Rep

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“…Human umbilical vein endothelial cells (HUVECs; ATCC) were cultured with EC medium (Sigma‐Aldrich) containing fetal bovine serum and penicillin/streptomycin, and the culture dish was placed at 37°C in a 5% CO 2 environment. The cells were treated with ox‐LDL (10 μg/mL) for 48 h to mimic AS, and pretreated with dendrobine (10 μM; Herbpurify) for 12 h. In the follow‐up mechanism study, cells were stimulated with mitophagy inhibitor Mdivi‐1 (10 μM; Selleck) for 2 h (Huang et al, 2022) or STAT3 agonist colivelin (1 μM; Selleck) for 24 h (Chen & Hou, 2022).…”

Section: Methodsmentioning

confidence: 99%

Dendrobine regulates STAT3 to attenuate mitochondrial dysfunction and senescence in vascular endothelial cells triggered by oxidized low‐density lipoprotein

Xia,

Chen,

Xing

et al. 2024

Drug Development Research

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Our previous studies have highlighted the potential therapeutic efficacy of dendrobine, an alkaloid, in atherosclerosis (AS), nevertheless, the underlying mechanism remains unclear. This study employs a combination of network pharmacology and in vitro experiments to explore the regulatory pathways involved. Through network pharmacology, the biological function for intersection targets between dendrobine and AS were identified. Molecular docking was conducted to investigate the interaction between the dominant target and dendrobine. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low‐density lipoprotein (ox‐LDL) to mimic AS, and the effects of dendrobine on cell viability, lipid deposition, mitochondrial function, and cellular senescence were evaluated. Subsequently, cells were treated with the mitophagy inhibitor Mdivi‐1 and the STAT3 agonist colivelin to assess the role of mitophagy and STAT3 signaling in dendrobine regulation. Intersection targets were associated with biological processes, including reactive oxygen species production. Dendrobine attenuated the effects of ox‐LDL treatment on HUVECs, mitigating changes in cell activity, lipid deposition, mitochondrial function, and cellular senescence. Both Mdivi‐1 and colivelin treatments resulted in decreased cell viability and increased cellular senescence, with colivelin suppressing mitophagy. Cotreatment with Mdivi‐1 and colivelin further aggravated cellular senescence and inhibited FoxO signaling. Together, this study indicated that dendrobine regulated the STAT3/FoxO signaling pathway, alleviating mitochondrial dysfunction and cellular senescence. This study contributes valuable insights to the potential clinical application of dendrobine.

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“…Mitochondrial reactive oxygen species (ROS) activity was detected using the fluorescent probe MitoSOX (Invitrogen). 33 Briefly, cardiomyocytes were incubated with 5 μM MitoSOX (red fluorescence) in PBS and DAPI (Beyotime Biotechnology, China) at 37°C in the dark for 10 minutes. The fluorescence intensity of mitochondria ROS probes was measured by fluorescence microscopy (Eclipse Ti-U, Nikon Corporation).…”

Section: Methodsmentioning

confidence: 99%

TRPV1 Protects Against Pressure Overload–Induced Cardiac Hypertrophy by Promoting Mitochondria-Associated Endoplasmic Reticulum Membranes

Wang

et al. 2022

Journal of Cardiovascular Pharmacology

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: Transient receptor potential vanilloid type 1 (TRPV1) is a nonselective cation channel that mediates the relationship between mitochondrial function and pathological myocardial hypertrophy. However, its underlying mechanisms remain unclear. This study aimed to investigate whether TRPV1 activation improves the morphology and function of intracellular mitochondria to protect cardiomyocytes after pressure overload-induced myocardial hypertrophy. The myocardial hypertrophy model was established by performing transverse aortic constriction surgery in C57BL/6 J male mice. The data revealed that TRPV1 activation significantly reduced myocardial hypertrophy, promoted ejection fraction% and fractional shortening%, and decreased the left ventricular internal diameter in end-diastole and left ventricular internal diameter in end-systole after transverse aortic constriction. Moreover, in vitro experiments revealed that TRPV1 reduces cardiomyocyte area and improves mitochondrial function by promoting mitochondria-associated endoplasmic reticulum membranes (MAMs) formation in a phenylephrine-treated cardiomyocyte hypertrophy model. TRPV1 up-regulates the phosphorylation levels of AMP-activated protein kinase and expression of mitofusin2 (MFN2). TRPV1 function is blocked by single-stranded RNA interfering with silent interfering MFN2. Activation of TRPV1 reduced mitochondrial reactive oxygen species caused by phenylephrine, whereas disruption of MAMs by siMFN2 abolished TRPV1-mediated mitochondrial protection. Our findings suggest that TRPV1 effectively protects against pressure overload-induced cardiac hypertrophy by promoting MAM formation and conserved mitochondrial function via the AMP-activated protein kinase/MFN2 pathway in cardiomyocytes.

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Impact of UCP2 depletion on heat stroke-induced mitochondrial function in human umbilical vein endothelial cells

Cited by 9 publications

References 44 publications

DNAJA1‑knockout alleviates heat stroke‑induced endothelial barrier disruption via improving thermal tolerance and suppressing the MLCK‑MLC signaling pathway

DNAJA1‑knockout alleviates heat stroke‑induced endothelial barrier disruption via improving thermal tolerance and suppressing the MLCK‑MLC signaling pathway

Dendrobine regulates STAT3 to attenuate mitochondrial dysfunction and senescence in vascular endothelial cells triggered by oxidized low‐density lipoprotein

TRPV1 Protects Against Pressure Overload–Induced Cardiac Hypertrophy by Promoting Mitochondria-Associated Endoplasmic Reticulum Membranes

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