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C-reactive protein accelerates DRP1-mediated mitochondrial fission by modulating ERK1/2-YAP signaling in cardiomyocytes

Authors
 Suyeon Jin  ;  Chan Joo Lee  ;  Gibbeum Lim  ;  Sungha Park  ;  Sang-Hak Lee  ;  Ji Hyung Chung  ;  Jaewon Oh  ;  Seok-Min Kang 
Citation
 BMB REPORTS, Vol.56(12) : 663-668, 2023-12 
Journal Title
BMB REPORTS
ISSN
 1976-6696 
Issue Date
2023-12
MeSH
C-Reactive Protein / metabolism ; C-Reactive Protein / pharmacology ; Dynamins* / metabolism ; MAP Kinase Signaling System ; Mitochondrial Dynamics / physiology ; Myocytes, Cardiac* ; Protein Kinases / metabolism ; Reactive Oxygen Species / metabolism ; Survivin / metabolism ; Survivin / pharmacology
Keywords
C-reactive protein ; Cardiomyocyte ; DRP1 ; Mitochondria ; Survivin
Abstract
C-reactive protein (CRP) is an inflammatory marker and risk factor for atherosclerosis and cardiovascular diseases. However, the mechanism through which CRP induces myocardial damage remains unclear. This study aimed to determine how CRP damages cardiomyocytes via the change of mitochondrial dynamics and whether survivin, an anti-apoptotic protein, exerts a cardioprotective effect in this process. We treated H9c2 cardiomyocytes with CRP and found increased intracellular ROS production and shortened mitochondrial length. CRP treatment phosphorylated ERK1/2 and promoted increased expression, phosphorylation, and translocation of DRP1, a mitochondrial fission-related protein, from the cytoplasm to the mitochondria. The expression of mitophagy proteins PINK1 and PARK2 was also increased by CRP. YAP, a transcriptional regulator of PINK1 and PARK2, was also increased by CRP. Knockdown of YAP prevented CRP-induced increases in DRP1, PINK1, and PARK2. Furthermore, CRP-induced changes in the expression of DRP1 and increases in YAP, PINK1, and PARK2 were inhibited by ERK1/2 inhibition, suggesting that ERK1/2 signaling is involved in CRP-induced mitochondrial fission. We treated H9c2 cardiomyocytes with a recombinant TAT-survivin protein before CRP treatment, which reduced CRP-induced ROS accumulation and reduced mitochondrial fission. CRP-induced activation of ERK1/2 and increases in the expression and activity of YAP and its downstream mitochondrial proteins were inhibited by TAT-survivin. This study shows that mitochondrial fission occurs during CRPinduced cardiomyocyte damage and that the ERK1/2-YAP axis is involved in this process, and identifies that survivin alters these mechanisms to prevent CRP-induced mitochondrial damage. [BMB Reports 2023; 56(12): 663-668].
Files in This Item:
T202400272.pdf Download
DOI
10.5483/BMBRep.2023-0127
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Seok Min(강석민) ORCID logo https://orcid.org/0000-0001-9856-9227
Park, Sung Ha(박성하) ORCID logo https://orcid.org/0000-0001-5362-478X
Oh, Jae Won(오재원) ORCID logo https://orcid.org/0000-0002-4585-1488
Lee, Sang Hak(이상학) ORCID logo https://orcid.org/0000-0002-4535-3745
Lee, Chan Joo(이찬주) ORCID logo https://orcid.org/0000-0002-8756-409X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/197853
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