ROS‐Autophagy pathway mediates monocytes‐human umbilical vein endothelial cells adhesion induced by apelin‐13

Liu, Meiqing; Li, Hening; Zhou, Qun; Zhao, Hong; Lv, Deguan; Cao, Jun; Jiang, Jinyong; Tang, Mingzhu; Wu, Di; Liu, Jiaqi; Wu, Lixian; Hu, Haoliang; He, Lu; Huang, Shifang; Chen, Zhe; Li, Lanfang; Chen, Linxi

doi:10.1002/jcp.26554

Cited by 24 publications

(20 citation statements)

References 53 publications

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“…The molecular mechanism underlying autophagy has been extensively investigated in recent years. The mitochondrial antioxidant Mito-TEMPO (mitochondrial-targeted SOD mimetic) enhanced SOD2 activity but not SOD2 levels, significantly suppressed the 5-ALA-PDT-mediated increase in autophagy level, and consistent with many studies revealed that ROS can induce autophagy [34] , [35] , [36] .…”

Section: Discussionsupporting

confidence: 83%

Efficacy of 5-aminolevulinic acid–based photodynamic therapy against keloid compromised by downregulation of SIRT1-SIRT3-SOD2-mROS dependent autophagy pathway

Liu

Ouyang

et al. 2019

Redox Biology

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Keloids exhibit cancer-like properties without spontaneous regression and usually recur post excision. Although photodynamic therapy (PDT) is a promising treatment, details of the mechanisms remain to be elucidated. In this study, we investigated mechanisms involved in 5-Aminolevulinic Acid (5-ALA)–based PDT against keloid. Found that 5-ALA-PDT induced superoxide anion-dependent autophagic cell death. Application of autophagy inhibitor 3-Methyladenine (3-MA) significantly prevented the effect that 5-ALA-PDT induced keloid–derived fibroblasts death, but Z-VAK-FMK (apoptotic inhibitor) did not. Interestingly, 5-ALA-PDT promoted the SIRT3 protein expression and the activity of mitochondrial superoxide dismutase 2 (SOD2), but SIRT1 protein expression level was decreased. SOD2 as a key enzyme can decrease mitochondrial ROS (mROS) level, Deacetylation of SOD2 by SIRT3 regulates SOD2 enzymatic activity has been identified. Then we explored SOD2 acetylation level with immunoprecipitation, found that 5-ALA-PDT significantly increased the acetylation levels of SOD2. In order to confirm deacetylation of SOD2 regulated by SIRT3, 3-TYP (SIRT3 inhibitor) was used. Found that inhibition of SIRT3 by 3-TYP significantly increased the level of SOD2 acetylation level compared with control group or 5-ALA-PDT group. To explore the connection of SIRT1 and SIRT3, cells were treated with EX527(SIRT1 inhibitor) or SRT1720 (SIRT1 activator), and EX527 increased SIRT3 protein level, however, SRT1720 displayed the opposite effect in the present or absence of 5-ALA-PDT. Moreover SIRT1-inhibited cells are more resistant to 5-ALA-PDT and showing decreased ROS accumulation. These results may demonstrate that 5-ALA-PDT induced SIRT1 protein level decreased, which promoted the effect of SIRT3 increased activity of SOD2 that can reduce mROS level, and then compromised 5-ALA-PDT induced autophagic cell death.

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Section: Discussionsupporting

confidence: 83%

Efficacy of 5-aminolevulinic acid–based photodynamic therapy against keloid compromised by downregulation of SIRT1-SIRT3-SOD2-mROS dependent autophagy pathway

Liu

Ouyang

et al. 2019

Redox Biology

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“…For example, a previous study demonstrates that apelin reduces oxidative stress and prevents pressure-overloadinduced left ventricular hypertrophy 44 . By contrast, there is increasing evidence proving that apelin-13 induces cardiac hypertrophy by increasing the production of ROS and the expression levels of NADPH oxidases in vivo and in vitro [45][46][47] . In addition, apelin/APJ in paraventricular nucleus is found to induce long-term high BP and renal sympathetic nerve activity via increasing oxidative stress 37,48 .…”

Section: Discussionmentioning

confidence: 98%

“…In addition, it is known that the regulatory effects of apelin on oxidative stress are conducted by binding to its receptor APJ in most experimental conditions 37,46,47 . As another endogenous ligand, it is still unclear whether ELA is dependent on APJ to suppress DOCA/salt-induced NADPH oxidase/ROS/NLRP3 signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

ELABELA attenuates deoxycorticosterone acetate/salt-induced hypertension and renal injury by inhibition of NADPH oxidase/ROS/NLRP3 inflammasome pathway

Chen

Liu

et al. 2020

Cell Death Dis

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ELABELA (ELA), a 32-residue hormone peptide abundantly expressed in adult kidneys, has been identified as a novel endogenous ligand for APJ/Apelin receptor. The aim of this study was to investigate the role of ELA in deoxycorticosterone acetate (DOCA)/salt-induced hypertension and further explore the underlying mechanism. In DOCA/salt-treated rats, the mRNA level of ELA greatly decreased in the renal medulla. Next, overexpression of ELA in the kidney was found to attenuate DOCA/salt-induced hypertension and renal injury, including lower blood pressure, reversed glomerular morphological damage, decreased blood urea nitrogen (BUN), and blocked the accumulation of fibrotic markers. Mechanistically, ELA overexpression inhibited renal nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and subsequent reactive oxygen species (ROS) production, thus resulted in the blockade of formation and activation of Nod-like receptor protein 3 (NLRP3) inflammasome. The inhibitory effects of ELA on Aldosterone-stimulated NADPH oxidase/ROS/NLRP3 inflammasome pathway were confirmed in the human renal tubular cells. Furthermore, our in vivo and in vitro results showed that the deficiency of the apelin receptor APJ did not influence the antihypertensive effect and blockage to NADPH oxidase/ROS/NLRP3 pathway of ELA. Moreover, in heterozygous ELA knockout mice (ELA+/−), the ELA deficiency remarkably accelerated the onset of DOCA/salt-induced hypertension. Our data demonstrate that ELA prevents DOCA/salt-induced hypertension by inhibiting NADPH oxidase/ROS/NLRP3 pathway in the kidney, which is APJ independent. Pharmacological targeting of ELA may serve as a novel therapeutic strategy for the treatment of hypertensive kidney disease.

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“…(f) Representative western blots analysis of Drp1, Mfn1, Mfn2, and OPA1 expressions in human aortic VSMC infected with siRNA AMPKα or siRNA scramble transfection (n = 3 *p < 0.05 and **p < 0.01 vs. control, # p < 0.01, ## p < 0.01 vs. apelin-13). CCK-8: cell counting kit-8; FBS: fetal bovine serum; PBS: phosphatebuffered saline; VMSC: vascular smooth muscle cell M. Liu et al, 2018). Moreover, it has been widely reported that apelin and APJ are upregulated in heart of hypertensive rats and human autopsy atherosclerotic coronary artery (Pitkin, Maguire, Kuc, & Davenport, 2010;Sekerci, Acar, Tepekoy, Ustunel, & Keles-Celik, 2018).…”

Section: Discussionmentioning

confidence: 99%

PINK1/Parkin‐mediated mitophagy promotes apelin‐13‐induced vascular smooth muscle cell proliferation by AMPKα and exacerbates atherosclerotic lesions

Zhou

Huang

et al. 2018

Journal Cellular Physiology

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Aberrant proliferation of vascular smooth muscle cells (VSMC) is a critical contributor to the pathogenesis of atherosclerosis (AS). Our previous studies have demonstrated that apelin‐13/APJ confers a proliferative response in VSMC, however, its underlying mechanism remains elusive. In this study, we aimed to investigate the role of mitophagy in apelin‐13‐induced VSMC proliferation and atherosclerotic lesions in apolipoprotein E knockout (ApoE‐/‐) mice. Apelin‐13 enhances human aortic VSMC proliferation and proliferative regulator proliferating cell nuclear antigen expression in dose and time‐dependent manner, while is abolished by APJ antagonist F13A. We observe the engulfment of damage mitochondria by autophagosomes (mitophagy) of human aortic VSMC in apelin‐13 stimulation. Mechanistically, apelin‐13 increases p‐AMPKα and promotes mitophagic activity such as the LC3I to LC3II ratio, the increase of Beclin‐1 level and the decrease of p62 level. Importantly, the expressions of PINK1, Parkin, VDAC1, and Tom20 are induced by apelin‐13. Conversely, blockade of APJ by F13A abolishes these stimulatory effects. Human aortic VSMC transfected with AMPKα, PINK1, or Parkin and subjected to apelin‐13 impairs mitophagy and prevents proliferation. Additional, apelin‐13 not only increases the expression of Drp1 but also reduces the expressions of Mfn1, Mfn2, and OPA1. Remarkably, the mitochondrial division inhibitor‐1(Mdivi‐1), the pharmacological inhibition of Drp1, attenuates human aortic VSMC proliferation. Treatment of ApoE‐/‐ mice with apelin‐13 accelerates atherosclerotic lesions, increases p‐AMPKα and mitophagy in aortic wall in vivo. Finally, PINK1‐/‐ mutant mice with apelin‐13 attenuates atherosclerotic lesions along with defective in mitophagy. PINK1/Parkin‐mediated mitophagy promotes apelin‐13‐evoked human aortic VSMC proliferation by activating p‐AMPKα and exacerbates the progression of atherosclerotic lesions.

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ROS‐Autophagy pathway mediates monocytes‐human umbilical vein endothelial cells adhesion induced by apelin‐13

Cited by 24 publications

References 53 publications

Efficacy of 5-aminolevulinic acid–based photodynamic therapy against keloid compromised by downregulation of SIRT1-SIRT3-SOD2-mROS dependent autophagy pathway

Efficacy of 5-aminolevulinic acid–based photodynamic therapy against keloid compromised by downregulation of SIRT1-SIRT3-SOD2-mROS dependent autophagy pathway

ELABELA attenuates deoxycorticosterone acetate/salt-induced hypertension and renal injury by inhibition of NADPH oxidase/ROS/NLRP3 inflammasome pathway

PINK1/Parkin‐mediated mitophagy promotes apelin‐13‐induced vascular smooth muscle cell proliferation by AMPKα and exacerbates atherosclerotic lesions

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