[Change of JNK MAPK and its influence on cardiocyte apoptosis in ischemic postconditioning].

Abstract

OBJECTIVE:

To test whether postconditioning could inhibit the expression of phospho-JNK (P-JNK) mitogen activated protein kinase (MAPK) and study its relation to apoptosis of cardiocyte.

METHODS:

Sixty rats were randomly divided into six groups: sham, reperfusion injury (R/I), postconditioning (Post), SP600125 (I_JNK), anisomycin and postconditioning (Ani+Post) and anisomycin (Ani) groups. After acute myocardial infarction was induced in rats, placebo solution (DMSO), SP600125 (6 mg/kg) or anisomycin (2 mg/kg) was injected through jugular vein 5 min before reperfusion; 6 h later 3 rats of each group were executed and the hearts were separated to measure the signaling molecules (phospho-JNK, TNF alpha, Caspase-8, Bcl-2/Bax, cytochrome-c). Twenty-two hours later hemodynamic data were measured in the left rats, and then blood samples were taken to determine serum markers of cardiac damage, and hearts were separated to measure the infarction area and cardiocyte apoptosis.

RESULT:

Postconditioning improved +/-DP/DTmax of left ventricle, limited infarct area, relieved apoptosis and necrosis of cardiocytes, and inhibited the expression of P-JNK (1.12 +/-0.21 Compared with 1.90 +/-0.32, P<0.05). At the same time the levels of TNFalpha Caspase-8, Bax and Cyt-c were lower in Post group than those in R/I group, but Bcl-2 expression levels were higher. I_JNK group presented the similar protection effect of postconditioning [TUNEL index: (6.23 +/-2.43)% Compared with (18.22 +/-5.10)%, P<0.05; Infarct area: (23.44 +/-6.34)% Compared with (42.31 +/-8.21)%, P<0.05]. On the other hand, Ani+Post group partially lost cardioprotection effect [TUNEL index: (14.12 +/-2.00)% Compared with (18.22 +/-5.10)%,P>0.05; Infarct area: (35.27 +/-5.28)% Compared with (42.31+/-8.21)%,P>0.05], because of the activation of JNK MAPK.

CONCLUSION:

Postconditioning can inhibit phosphorylation of JNK MAPK, which attenuates cardiocyte apoptosis by both extrinsic and mitochondria pathway.

• Authors: Guo-Ming Zhang, Yu Wang, Tian-de Li, Da-Wei Zhang, Xiu-Hua Liu, Fei-Fei Yang
• Journal: Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences (Zhejiang Da Xue Xue Bao Yi Xue Ban) Vol. 38 Issue 6 Pg. 611-9 (11 2009) ISSN: 1008-9292 [Print] China
• PMID: 20014487 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• JNK Mitogen-Activated Protein Kinases

Topics

• Animals
• Apoptosis (drug effects)
• Ischemic Preconditioning, Myocardial
• JNK Mitogen-Activated Protein Kinases (metabolism, pharmacology)
• Male
• Myocardial Infarction (enzymology, pathology, therapy)
• Myocardial Reperfusion Injury (prevention & control)
• Myocytes, Cardiac (enzymology, pathology)
• Random Allocation
• Rats
• Rats, Sprague-Dawley