PMID- 23680658
OWN - NLM
STAT- MEDLINE
DCOM- 20131025
LR  - 20211021
IS  - 2092-6413 (Electronic)
IS  - 1226-3613 (Print)
IS  - 1226-3613 (Linking)
VI  - 45
IP  - 5
DP  - 2013 May 17
TI  - Inhibition of Janus activated kinase-3 protects against myocardial ischemia and 
      reperfusion injury in mice.
PG  - e23
LID - 10.1038/emm.2013.43 [doi]
AB  - Recent studies have documented that Janus-activated kinase (JAK)-signal 
      transducer and activator of transcription (STAT) pathway can modulate the 
      apoptotic program in a myocardial ischemia/reperfusion (I/R) model. To date, 
      however, limited studies have examined the role of JAK3 on myocardial I/R injury. 
      Here, we investigated the potential effects of pharmacological JAK3 inhibition 
      with JANEX-1 in a myocardial I/R model. Mice were subjected to 45 min of ischemia 
      followed by varying periods of reperfusion. JANEX-1 was injected 1 h before 
      ischemia by intraperitoneal injection. Treatment with JANEX-1 significantly 
      decreased plasma creatine kinase and lactate dehydrogenase activities, reduced 
      infarct size, reversed I/R-induced functional deterioration of the myocardium and 
      reduced myocardial apoptosis. Histological analysis revealed an increase in 
      neutrophil and macrophage infiltration within the infarcted area, which was 
      markedly reduced by JANEX-1 treatment. In parallel, in in vitro studies where 
      neutrophils and macrophages were treated with JANEX-1 or isolated from JAK3 
      knockout mice, there was an impairment in the migration potential toward 
      interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), 
      respectively. Of note, however, JANEX-1 did not affect the expression of IL-8 and 
      MCP-1 in the myocardium. The pharmacological inhibition of JAK3 might represent 
      an effective approach to reduce inflammation-mediated apoptotic damage initiated 
      by myocardial I/R injury.
FAU - Oh, Young-Bin
AU  - Oh YB
AD  - Department of Physiology, Chonbuk National University Medical School, Jeonju, 
      Jeonbuk, Republic of Korea.
FAU - Ahn, Min
AU  - Ahn M
FAU - Lee, Sang-Myeong
AU  - Lee SM
FAU - Koh, Hyoung-Won
AU  - Koh HW
FAU - Lee, Sun-Hwa
AU  - Lee SH
FAU - Kim, Suhn Hee
AU  - Kim SH
FAU - Park, Byung-Hyun
AU  - Park BH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130517
PL  - United States
TA  - Exp Mol Med
JT  - Experimental & molecular medicine
JID - 9607880
RN  - 0 (Chemokines)
RN  - 0 (Quinazolines)
RN  - 0 (WHI P131)
RN  - EC 2.7.10.2 (Jak3 protein, mouse)
RN  - EC 2.7.10.2 (Janus Kinase 3)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Cell Movement/drug effects
MH  - Chemokines/pharmacology
MH  - Heart Function Tests/drug effects
MH  - Inflammation/pathology
MH  - Janus Kinase 3/*antagonists & inhibitors/metabolism
MH  - Macrophages/drug effects/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myocardial Reperfusion Injury/drug 
      therapy/*enzymology/physiopathology/*prevention & control
MH  - Myocardium/enzymology/pathology
MH  - Myocytes, Cardiac/drug effects/metabolism/pathology
MH  - Neutrophils/drug effects/metabolism/pathology
MH  - Quinazolines/pharmacology/therapeutic use
PMC - PMC3674406
EDAT- 2013/05/18 06:00
MHDA- 2013/10/26 06:00
PMCR- 2013/05/01
CRDT- 2013/05/18 06:00
PHST- 2013/05/18 06:00 [entrez]
PHST- 2013/05/18 06:00 [pubmed]
PHST- 2013/10/26 06:00 [medline]
PHST- 2013/05/01 00:00 [pmc-release]
AID - emm201343 [pii]
AID - 10.1038/emm.2013.43 [doi]
PST - epublish
SO  - Exp Mol Med. 2013 May 17;45(5):e23. doi: 10.1038/emm.2013.43.