SRV2 promotes mitochondrial fission and Mst1-Drp1 signaling in LPS-induced septic cardiomyopathy

Shang, Xiuling; Zhang, Yingrui; Xu, Jiaqi; Li, Min; Wang, Xiaoting; Yu, Rongguo

doi:10.18632/aging.102691

Cited by 17 publications

(7 citation statements)

References 72 publications

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“…Transcription of mitochondrial fission-related proteins, including Drp1 and Fis1, increases rapidly after exposure to LPS. [39,40] In addition, suppression of DRP1-mediated mitochondrial fission selectively blocks the release of Cyt-C during apoptosis. [41] In our study, OCA significantly suppressed LPSinduced expression of p-DRP1 and release of Cyt-C. OCA pretreatment inhibited the LPS-induced mitochondrial dysfunction, which may be attributed to the inhibition of Drp1 phosphorylation, limiting mitochondrial fragmentation and enhancing the degradation of damaged mitochondria.…”

Section: Discussionmentioning

confidence: 99%

Obeticholic Acid Inhibit Mitochondria Dysfunction Via Regulating ERK1/2‐DRP Pathway to Exert Protective Effect on Lipopolysaccharide‐Induced Myocardial Injury

Miao,

Tang,

Cui

et al. 2024

Advanced Biology

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Farnesoid X receptor (FXR) plays critical regulatory roles in cardiovascular physiology/pathology. However, the role of FXR agonist obeticholic acid (OCA) in sepsis‐associated myocardial injury and underlying mechanisms remain unclear. C57BL/6J mice are treated with OCA before lipopolysaccharide (LPS) administration. The histopathology of the heart and assessment of FXR expression and mitochondria function are performed. To explore the underlying mechanisms, H9c2 cells, and primary cardiomyocytes are pre‐treated with OCA before LPS treatment, and extracellular signal‐regulated protein kinase (ERK) inhibitor PD98059 is used. LPS‐induced myocardial injury in mice is significantly improved by OCA pretreatment. Mechanistically, OCA pretreatment decreased reactive oxygen species (ROS) levels and blocked the loss of mitochondrial membrane potential (ΔΨm) in cardiomyocytes. The expression of glutathione peroxidase 1 (GPX1), superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2), and nuclear factor erythroid 2‐related factor 2 (NRF‐2) increased in the case of OCA pretreatment. In addition, OCA improved mitochondria respiratory chain with increasing Complex I expression and decreasing cytochrome C (Cyt‐C) diffusion. Moreover, OCA pretreatment inhibited LPS‐induced mitochondria dysfunction via suppressing ERK1/2‐DRP signaling pathway. FXR agonist OCA inhibits LPS‐induced mitochondria dysfunction via suppressing ERK1/2‐DRP signaling pathway to protect mice against LPS‐induced myocardial injury.

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Section: Discussionmentioning

confidence: 99%

Obeticholic Acid Inhibit Mitochondria Dysfunction Via Regulating ERK1/2‐DRP Pathway to Exert Protective Effect on Lipopolysaccharide‐Induced Myocardial Injury

Miao,

Tang,

Cui

et al. 2024

Advanced Biology

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“…According to the previous literature, SIC models were constructed on mice by abdominal injection of LPS. 17 Prior to the experiment, all mice were fasted for 12 h but could drink freely and then injected abdominally with LPS at dose of 10 mg/kg body weight dissolved in saline, while for the mice in the control group ( n = 12), LPS was substituted by the normal saline. The models were divided randomly into the LPS group, LPS + pre-miR-141 group, and LPS + anti-miR-141 group, with 12 mice in each group.…”

Section: Methodsmentioning

confidence: 99%

MiR-141 attenuates sepsis-induced cardiomyopathy by targeting DAPK1

Song

Wang²,

Yang

et al. 2021

Hum Exp Toxicol

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Objective To discuss the possible effects of microRNA-141 (miR-141) in sepsis-induced cardiomyopathy (SIC) via targeting death-associated protein kinase 1 (DAPK1). Methods An SIC mouse model was constructed by abdominal injection of lipopolysaccharide (LPS) and divided into control, LPS, LPS + pre-miR-141, and LPS + anti-miR-141 groups. Hemodynamic indicators and heart function indexes of mice were detected. ELISA was used to determine the serum levels of inflammatory cytokines, while TUNEL staining to observe the apoptosis of myocardial cells of mice, as well as qRT-PCR and Western blotting to clarify the expression of miR-141 and DAPK1. Lastly, in vitro experiment was also conducted on the primary neonatal rat ventricular cardiomyocytes (NRVCMs) to validate the results. Results Mice in the LPS group, as compared to the control group, had lower left ventricular ejection fraction, left ventricular fractional shortening, left ventricular systolic pressure, and ±dp/dt, but a higher left ventricular end-diastolic pressure, while the serum expression of IL-1β, IL-6, TNF-α, and cTn-T was up-regulated evidently with the increased apoptotic index of myocardial tissues. However, miR-141 and Bcl-2/Bax were down-regulated with elevated DAPK1 and cleaved caspase-3. The above changes were ameliorated in mice from the LPS + pre-miR-141 group relative to the LPS group, while those in the LPS + anti-miR-141 group were further deteriorated. In vitro experiment showed that miR-141 overexpression could reduce the apoptosis of LPS-induced NRVCMs and the levels of inflammatory cytokines with the increased cell viability. Conclusion MiR-141 could decrease inflammatory response and reduce myocardial cell apoptosis by targeting DAPK1, thereby playing the promising protective role in SIC.

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“…Furthermore, cyclase-associated protein (CAP) are recently discovered split-promoting proteins that induce the oligomerization of DRP1 and the expression of FIS1, which promotes DRP1-mediated mitochondrial fission ( 55 ).…”

Section: The Physiological State Of Mitochondrial Dynamics and Mitophagymentioning

confidence: 99%

Advances in Cardiotoxicity Induced by Altered Mitochondrial Dynamics and Mitophagy

Yin

Shen

2021

Front. Cardiovasc. Med.

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Mitochondria are the most abundant organelles in cardiac cells, and are essential to maintain the normal cardiac function, which requires mitochondrial dynamics and mitophagy to ensure the stability of mitochondrial quantity and quality. When mitochondria are affected by continuous injury factors, the balance between mitochondrial dynamics and mitophagy is broken. Aging and damaged mitochondria cannot be completely removed in cardiac cells, resulting in energy supply disorder and accumulation of toxic substances in cardiac cells, resulting in cardiac damage and cardiotoxicity. This paper summarizes the specific underlying mechanisms by which various adverse factors interfere with mitochondrial dynamics and mitophagy to produce cardiotoxicity and emphasizes the crucial role of oxidative stress in mitophagy. This review aims to provide fresh ideas for the prevention and treatment of cardiotoxicity induced by altered mitochondrial dynamics and mitophagy.

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SRV2 promotes mitochondrial fission and Mst1-Drp1 signaling in LPS-induced septic cardiomyopathy

Cited by 17 publications

References 72 publications

Obeticholic Acid Inhibit Mitochondria Dysfunction Via Regulating ERK1/2‐DRP Pathway to Exert Protective Effect on Lipopolysaccharide‐Induced Myocardial Injury

Obeticholic Acid Inhibit Mitochondria Dysfunction Via Regulating ERK1/2‐DRP Pathway to Exert Protective Effect on Lipopolysaccharide‐Induced Myocardial Injury

MiR-141 attenuates sepsis-induced cardiomyopathy by targeting DAPK1

Advances in Cardiotoxicity Induced by Altered Mitochondrial Dynamics and Mitophagy

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