PMID- 30792486
OWN - NLM
STAT- MEDLINE
DCOM- 20191223
LR  - 20220416
IS  - 1745-7254 (Electronic)
IS  - 1671-4083 (Print)
IS  - 1671-4083 (Linking)
VI  - 40
IP  - 8
DP  - 2019 Aug
TI  - Minocycline protects against myocardial ischemia/reperfusion injury in rats by 
      upregulating MCPIP1 to inhibit NF-kappaB activation.
PG  - 1019-1028
LID - 10.1038/s41401-019-0214-z [doi]
AB  - Minocycline is a tetracycline antibiotic and has been shown to play a protective 
      role in cerebral and myocardial ischemia/reperfusion (I/R). However, the 
      underlying mechanism remains unclear. Herein, we investigated whether monocyte 
      chemotactic protein-induced protein-1 (MCPIP1), a negative regulator of 
      inflammation, was involved in the minocycline-induced cardioprotection in 
      myocardial I/R in vivo and in vitro models. Myocardial ischemia was induced in 
      rats by left anterior descending coronary artery occlusion for 1 h and followed 
      by 48 h reperfusion. Minocycline was administered prior to ischemia (45 mg/kg, 
      ip, BID, for 1 d) and over the course of reperfusion (22.5 mg/kg, ip, BID, for 
      2 d). Cardiac function and infarct sizes were assessed. Administration of 
      minocycline significantly decreased the infarct size, alleviated myocardial cell 
      damage, elevated left ventricle ejection fraction, and left ventricle fractional 
      shortening following I/R injury along with significantly decreased 
      pro-inflammatory cytokine IL-1beta and monocyte chemoattractant protein-1 (MCP-1) 
      levels in heart tissue. H9c2 cardiomyocytes were subjected to oxygen glucose 
      deprivation (OGD) followed by reoxygenation (OGD/R). Pretreatment with 
      minocycline (1-50 mumol/L) dose-dependently increased the cell viability and 
      inhibited OGD/R-induced expression of MCP-1 and IL-6. Furthermore, minocycline 
      dose-dependently inhibited nuclear translocation of NF-kappaB p65 in H9c2 cells 
      subjected to OGD/R. In both the in vivo and in vitro models, minocycline 
      significantly increased MCPIP1 protein expression; knockdown of MCPIP1 with siRNA 
      in H9c2 cells abolished all the protective effects of minocycline against 
      OGD/R-induced injury. Our results demonstrate that minocycline alleviates 
      myocardial I/R injury via upregulating MCPIP1, then subsequently inhibiting NF-kappaB 
      activation and pro-inflammatory cytokine secretion.
FAU - Yi, Quan
AU  - Yi Q
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Guangzhou Medical 
      University, Guangzhou 510182, China.
FAU - Tan, Fang-Hui
AU  - Tan FH
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Guangzhou Medical 
      University, Guangzhou 510182, China.
FAU - Tan, Jia-An
AU  - Tan JA
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Guangzhou Medical 
      University, Guangzhou 510182, China.
FAU - Chen, Xiu-Hui
AU  - Chen XH
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Guangzhou Medical 
      University, Guangzhou 510182, China.
FAU - Xiao, Qing
AU  - Xiao Q
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Guangzhou Medical 
      University, Guangzhou 510182, China.
FAU - Liu, Ying-Hua
AU  - Liu YH
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Guangzhou Medical 
      University, Guangzhou 510182, China.
FAU - Zhang, Gui-Ping
AU  - Zhang GP
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Guangzhou Medical 
      University, Guangzhou 510182, China.
FAU - Luo, Jian-Dong
AU  - Luo JD
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Guangzhou Medical 
      University, Guangzhou 510182, China. jiandongluo@hotmail.com.
AD  - Guangzhou Institute of Cardiovascular Disease, Guangzhou Key Laboratory of 
      Cardiovascular Disease, Second Affiliated Hospital, Guangzhou Medical University, 
      Guangzhou 510260, China. jiandongluo@hotmail.com.
LA  - eng
PT  - Journal Article
DEP - 20190221
PL  - United States
TA  - Acta Pharmacol Sin
JT  - Acta pharmacologica Sinica
JID - 100956087
RN  - 0 (Cardiotonic Agents)
RN  - 0 (Cytokines)
RN  - 0 (NF-kappa B)
RN  - EC 3.1.- (Ribonucleases)
RN  - EC 3.1.- (Zc3h12a protein, rat)
RN  - FYY3R43WGO (Minocycline)
SB  - IM
MH  - Animals
MH  - Cardiotonic Agents/*pharmacology
MH  - Cell Line
MH  - Cytokines/metabolism
MH  - Male
MH  - Minocycline/*pharmacology
MH  - Myocardial Reperfusion Injury/*prevention & control
MH  - NF-kappa B/*antagonists & inhibitors
MH  - Rats, Sprague-Dawley
MH  - Ribonucleases/genetics/*metabolism
MH  - Up-Regulation
PMC - PMC6786388
OTO - NOTNLM
OT  - H9c2 cardiomyocytes
OT  - NF-kappaB
OT  - cytokine
OT  - minocycline
OT  - monocyte chemotactic protein-induced protein-1
OT  - myocardial ischemia and reperfusion
OT  - oxygen glucose deprivation
COIS- None
EDAT- 2019/02/23 06:00
MHDA- 2019/12/24 06:00
PMCR- 2020/08/01
CRDT- 2019/02/23 06:00
PHST- 2018/11/05 00:00 [received]
PHST- 2019/01/16 00:00 [accepted]
PHST- 2019/02/23 06:00 [pubmed]
PHST- 2019/12/24 06:00 [medline]
PHST- 2019/02/23 06:00 [entrez]
PHST- 2020/08/01 00:00 [pmc-release]
AID - 10.1038/s41401-019-0214-z [pii]
AID - 214 [pii]
AID - 10.1038/s41401-019-0214-z [doi]
PST - ppublish
SO  - Acta Pharmacol Sin. 2019 Aug;40(8):1019-1028. doi: 10.1038/s41401-019-0214-z. 
      Epub 2019 Feb 21.