PMID- 34921980
OWN - NLM
STAT- MEDLINE
DCOM- 20220331
LR  - 20220531
IS  - 1873-3913 (Electronic)
IS  - 0898-6568 (Linking)
VI  - 91
DP  - 2022 Mar
TI  - BI-1 ameliorates myocardial injury by activating the mitochondrial unfolded 
      protein response and FUNDC1-related mitophagy in cardiorenal syndrome type 3.
PG  - 110218
LID - S0898-6568(21)00307-7 [pii]
LID - 10.1016/j.cellsig.2021.110218 [doi]
AB  - It has been suggested that mitochondrial dysfunction underlies the myocardial 
      injury seen following cardiorenal syndrome type 3 (CRS-3). Both mitophagy and the 
      mitochondrial unfolded protein response (UPR(mt)) are protective programs that 
      preserve mitochondrial homeostasis. Here, we explored whether Bax inhibitor-1 
      (BI-1) overexpression attenuates CRS-3-related myocardial injury through 
      activation of mitophagy and the UPR(mt) in cardiomyocytes. Following CRS-3 
      induction via renal ischemia-reperfusion injury, BI-1 transgenic (BI1(TG)) mice 
      showed greater preservation of myocardial integrity and relaxation function and 
      less cardiomyocyte apoptosis than wild-type (WT) mice. Moreover, BI-1 
      overexpression attenuated CRS-3-mediated myocardial inflammation, as indicated by 
      decreased MCP-1 and IL-6 expression and normalized ATP production in 
      cardiomyocytes. After CRS-3 induction, mitophagy was inhibited in cardiomyocytes 
      from WT mice, as indicated by both decreased Fundc1 transcription and mt-Keima 
      fluorescence, and modest activation of the UPR(mt), denoted by a slight increase 
      in Atf6 mRNA levels. By contrast, activation of mitophagy and marked UPR(mt) 
      upregulation were observed in cardiac tissue from BI1(TG) mice. shRNA-mediated 
      silencing of Fundc1 or Atf6 greatly impaired mitochondrial metabolism and 
      survival in cultured cardiomyocytes overexpressing BI-1. Thus, upregulation of 
      BI-1 expression aimed at activating mitophagy and the UPR(mt) may represent a 
      useful therapeutic approach for the treatment of CRS-3.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Wang, Jin
AU  - Wang J
AD  - Department of Vascular Medicine, Peking University Shougang Hospital, Beijing 
      100144, China. Electronic address: nkuwangjin@163.com.
FAU - Wang, Xiaohua
AU  - Wang X
AD  - National Clinical Research Center for Geriatric Diseases, People's Liberation 
      Army General Hospital, Beijing, China.
FAU - Du, Wenjuan
AU  - Du W
AD  - Laboratory of Radiation Injury Treatment, Medical Innovation Research Division, 
      Chinese People's Liberation Army General Hospital, Beijing, China.
FAU - Xue, Zhe
AU  - Xue Z
AD  - Department of Orthopedics, Peking University Shougang Hospital, Beijing 100144, 
      China.
FAU - Huang, Wei
AU  - Huang W
AD  - Department of Vascular Medicine, Peking University Shougang Hospital, Beijing 
      100144, China.
FAU - Guan, Zhenpeng
AU  - Guan Z
AD  - Department of Orthopedics, Peking University Shougang Hospital, Beijing 100144, 
      China.
FAU - Wang, Hongyu
AU  - Wang H
AD  - Department of Vascular Medicine, Peking University Shougang Hospital, Beijing 
      100144, China. Electronic address: dr.hongyuwang@foxmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211216
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (FUNDC1 protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Tmbim6 protein, mouse)
SB  - IM
MH  - Animals
MH  - *Cardio-Renal Syndrome
MH  - *Membrane Proteins/genetics/metabolism
MH  - Mice
MH  - *Mitochondrial Proteins/genetics/metabolism
MH  - *Mitophagy/physiology
MH  - Unfolded Protein Response
OTO - NOTNLM
OT  - Bax inhibitor-1 (BI-1)
OT  - Cardiomyocyte metabolism
OT  - Cardiorenal syndrome type 3
OT  - Mitochondrial unfolded protein response
OT  - Mitophagy
EDAT- 2021/12/19 06:00
MHDA- 2022/04/01 06:00
CRDT- 2021/12/18 20:15
PHST- 2021/11/10 00:00 [received]
PHST- 2021/12/10 00:00 [revised]
PHST- 2021/12/11 00:00 [accepted]
PHST- 2021/12/19 06:00 [pubmed]
PHST- 2022/04/01 06:00 [medline]
PHST- 2021/12/18 20:15 [entrez]
AID - S0898-6568(21)00307-7 [pii]
AID - 10.1016/j.cellsig.2021.110218 [doi]
PST - ppublish
SO  - Cell Signal. 2022 Mar;91:110218. doi: 10.1016/j.cellsig.2021.110218. Epub 2021 
      Dec 16.