PMID- 21610568
OWN - NLM
STAT- MEDLINE
DCOM- 20120202
LR  - 20131121
IS  - 1540-0514 (Electronic)
IS  - 1073-2322 (Linking)
VI  - 36
IP  - 3
DP  - 2011 Sep
TI  - Calcineurin mediates the protective effect of postconditioning on skeletal 
      muscle.
PG  - 312-6
LID - 10.1097/SHK.0b013e318224132e [doi]
AB  - We aimed to investigate whether ischemic postconditioning (I-postC) protects 
      skeletal muscle against ischemia-reperfusion (I/R) injury through the calcineurin 
      (CaN) pathway. Male Wistar rats underwent 4 h of right-hind-limb ischemia induced 
      by clamping the femoral artery, then reperfusion for 2 h (I/R-2 h), 12 h (I/R-12 
      h), or 24 h (I/R-24 h) with or without I-postC. Ischemic postconditioning was 
      induced by three cycles of 1-min reperfusion and 1-min ischemia at the onset of 
      reperfusion after prolonged ischemia. The I-postC-24 h group was treated with or 
      without cyclosporine A (a CaN inhibitor) 10 mg/kg per day for 3 days before 
      artery occlusion. Cultured skeletal muscle cells (SMCs) from neonatal rats were 
      exposed to 2-h hypoxia then 24-h reoxygenation (H/R), then postconditioned with 
      two cycles of 10-min reoxygenation and 10-min hypoxia after prolonged hypoxia 
      (hypoxia postconditioning [H-postC]) in the presence or absence of cyclosporine 
      A. We observed the effects of activated CaN overexpression on apoptosis and 
      viability of SMCs under H-postC. Ischemic postconditioning attenuated the 
      increase in the level of malondialdehyde in skeletal muscle induced by I/R-2 h 
      and I/R-24 h (P < 0.05) and lactate dehydrogenase in plasma induced by I/R-12 h 
      and I/R-24 h (P < 0.05). Cyclosporine A abolished the protective role of I-postC 
      in malondialdehyde level and lactate dehydrogenase leakage (P < 0.05, vs. I-postC 
      group). Hypoxia postconditioning suppressed SMC apoptosis induced by H/R (P < 
      0.05, vs. H/R), which was accompanied by increased CaN expression. Cyclosporine A 
      abolished the antiapoptotic effect of H-postC on SMCs (P < 0.05, vs. H-postC 
      group). Overexpression of activated CaN strengthened the cytoprotection of 
      H-postC (P < 0.05, vs. H-postC group). Ischemic postconditioning may protect 
      skeletal muscle against I/R injury through the CaN pathway.
FAU - Guo, Xiao-Sun
AU  - Guo XS
AD  - Department of Pathophysiology, Medicine School of Shandong University, Jinan, 
      China.
FAU - Li, Yu-Zhen
AU  - Li YZ
FAU - Liu, Xiu-Hua
AU  - Liu XH
FAU - Zhang, Zhen-Ying
AU  - Zhang ZY
FAU - Liu, Feng-Ying
AU  - Liu FY
FAU - Hu, Wei-Cheng
AU  - Hu WC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Shock
JT  - Shock (Augusta, Ga.)
JID - 9421564
RN  - 4Y8F71G49Q (Malondialdehyde)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - EC 3.1.3.16 (Calcineurin)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Apoptosis/drug effects/genetics
MH  - Blotting, Western
MH  - Calcineurin/*metabolism
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Cyclosporine/therapeutic use
MH  - Flow Cytometry
MH  - *Ischemic Preconditioning, Myocardial
MH  - Male
MH  - Malondialdehyde/metabolism
MH  - Muscle, Skeletal/drug effects/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Reperfusion Injury/metabolism/*prevention & control
EDAT- 2011/05/26 06:00
MHDA- 2012/02/03 06:00
CRDT- 2011/05/26 06:00
PHST- 2011/05/26 06:00 [entrez]
PHST- 2011/05/26 06:00 [pubmed]
PHST- 2012/02/03 06:00 [medline]
AID - 10.1097/SHK.0b013e318224132e [doi]
PST - ppublish
SO  - Shock. 2011 Sep;36(3):312-6. doi: 10.1097/SHK.0b013e318224132e.