PMID- 33986684
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210516
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 12
DP  - 2021
TI  - Capsaicin protects cardiomyocytes against lipopolysaccharide-induced damage via 
      14-3-3gamma-mediated autophagy augmentation.
PG  - 659015
LID - 10.3389/fphar.2021.659015 [doi]
LID - 659015
AB  - Background: The myocardium is susceptible to lipopolysaccharide (LPS)-induced 
      damage in sepsis, and cardiac dysfunction is a leading cause of mortality in 
      patients with sepsis. The changes in cardiomyocyte autophagy in sepsis and the 
      effects and mechanism of action of capsaicin (Cap) remain unclear. Methods and 
      Results: The potential pathway of 14-3-3gamma-dependent autophagy and the effects and 
      mechanisms of Cap were studied in LPS-induced injury to primary cultured neonatal 
      rat cardiomyocytes. The results showed that cardiomyocyte viability decreased, 
      lactate dehydrogenase and creatine kinase activities increased, 14-3-3gamma 
      expression was downregulated, and autophagy was inhibited after LPS challenge. 
      Cap pretreatment augmented autophagy by upregulating 14-3-3gamma expression and 
      activating AMP-activated protein kinase (AMPK) and unc-51 like 
      autophagy-activating kinase 1 (ULK1), suppressing mammalian target of rapamycin 
      (mTOR), alleviating cardiac dysfunction and improving the inflammation response, 
      whereas pAD/14-3-3gamma-shRNA nullified the above effects. Cap pretreatment also 
      decreased the levels of IL-1beta, TNF-alpha, IL-6, and IL-10; suppressed intracellular 
      oxidative stress; reduced the intracellular/mitochondrial reactive oxygen species 
      (ROS); balanced GSH/GSSG; increased GSH-Px, catalase, and SOD activities; and 
      decreased MDA contents. It also increased ATP content, activated complex Ⅰ and 
      complex Ⅲ, stabilized the mitochondrial membrane potential, and decreased the 
      mitochondrial permeability transition pore opening, thereby improving 
      mitochondrial function. Conclusion: Pretreatment with Cap can regulate autophagy 
      by upregulating 14-3-3gamma expression, inhibiting oxidative stress and inflammation, 
      maintaining mitochondrial function, and protecting cardiomyocytes against 
      LPS-induced injury.
CI  - Copyright (c) 2021 Qiao, Wang, Hu, Yin, He and He.
FAU - Qiao, Yang
AU  - Qiao Y
AD  - Institute of Cardiovascular Diseases, Jiangxi Academy of Clinical Medical 
      Sciences, The First Affiliated Hospital of Nanchang University, Nanchang, China.
FAU - Wang, Liang
AU  - Wang L
AD  - Department of Rehabilitation, The First Affiliated Hospital of Nanchang 
      University, Nanchang, China.
FAU - Hu, Tianhong
AU  - Hu T
AD  - Jiangxi Provincial Key Laboratory of Basic Pharmacology, Nanchang University 
      School of Pharmaceutical Science, Nanchang, China.
FAU - Yin, Dong
AU  - Yin D
AD  - Jiangxi Provincial Key Laboratory of Molecular Medicine, The Second Affiliated 
      Hospital, Nanchang University, Nanchang, China.
FAU - He, Huan
AU  - He H
AD  - Jiangxi Provincial Key Laboratory of Basic Pharmacology, Nanchang University 
      School of Pharmaceutical Science, Nanchang, China.
FAU - He, Ming
AU  - He M
AD  - Institute of Cardiovascular Diseases, Jiangxi Academy of Clinical Medical 
      Sciences, The First Affiliated Hospital of Nanchang University, Nanchang, China.
LA  - eng
PT  - Journal Article
DEP - 20210427
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC8111444
OTO - NOTNLM
OT  - 14-3-3gamma
OT  - Autophagy
OT  - Capsaicin
OT  - Cardiac dysfunction
OT  - Mitochondria
OT  - lipopolysaccharide
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/05/15 06:00
MHDA- 2021/05/15 06:01
PMCR- 2021/04/27
CRDT- 2021/05/14 06:57
PHST- 2021/01/26 00:00 [received]
PHST- 2021/03/30 00:00 [accepted]
PHST- 2021/05/14 06:57 [entrez]
PHST- 2021/05/15 06:00 [pubmed]
PHST- 2021/05/15 06:01 [medline]
PHST- 2021/04/27 00:00 [pmc-release]
AID - 659015 [pii]
AID - 10.3389/fphar.2021.659015 [doi]
PST - epublish
SO  - Front Pharmacol. 2021 Apr 27;12:659015. doi: 10.3389/fphar.2021.659015. 
      eCollection 2021.