[Study on crosstalk between phosphatidylinositol 3 -kinase/Akt pathway and p38 mitogen-activated protein kinase pathway in cardiomyocyte with challenge of burn serum].
OBJECTIVE
To investigate the possibility of crosstalk between phosphatidylinositol 3-kinase (PI3-K)/Akt pathway and p38 mitogen-activated protein kinase (p38MAPK) pathway in cardiomyocyte with challenge of burn serum, and to explore their influence on cardiomyocyte injury after burn.


METHODS
The model of murine cardiomyocyte with stimulation of burn serum was established. (1) The level of Akt and p38 phosphorylation in cardiomyocyte were examined with stimulation of 10% burn serum before stimulation and 1, 3, 6, 12, 24 hour after stimulation. (2) The levels of Akt and p38 phosphorylation in cardiomyocyte were determined with stimulation of burn serum (at concentration of 5%, 10%, 20%) or 10% burn serum plus insulin (at concentration of 1 x 10(-8), 1 x 10(-7), 1 x 10(-6)mol/L). The content of creatine kinase (CK) in supernate was also detected. (3) Addition to the inhibitor of p38 MAPK pathway (SB203580) and PI3K/Akt pathway (LY294002), the level of p38MAPK, PI3K/Akt and the content of CK in supernate were determined.


RESULTS
(1) The level of p-p38 in cardiomyocyte was 4.0 +/- 0.8, 3.6 +/- 0.8, 5.1 +/- 1.6, 2.4 +/- 0.5, 3.0 +/- 0.6 at 1, 3, 6, 12, 24 hour (s) after stimulation of burn serum, which was obviously higher than that immediate after stimulation (1.0, P < 0.01). The level of p-Akt was 0.15 +/- 0.07, 0.64 +/- 0.10, 0.26 +/- 0.08, 0.38 +/- 0.11, 0.59 +/- 0.13, which was obviously lower than that before stimulation (1.00, P < 0.01). (2) With stimulation of different concentration of burn serum or burn serum plus insulin, the level of p-Akt and p-p38 changed in the opposite directions comparatively. The content of CK increased along with increase of burn serum concentration, but decreased obviously with treatment of insulin (P < 0.05 or 0.01). (3) Low level of p38 induced by burn serum was increased after treatment of LY294002, which neutralized the protection of insulin (P < 0.01). Low level of p-Akt induced by burn serum increased after treatment of SB203580 (P < 0.01), which inhibited the release of CK induced by burn serum.


CONCLUSIONS
There is being crosstalk between PI3K/Akt pathway and p38 MAPK pathway in cardiomyocytes with challenge of burn serum, which may regulate cardiomyocytes.
Lv
Gen-fa
GF
Burn Center of PLA, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, PR China.
Chen
Bi
B
Zhang
Wan-fu
WF
Wang
Yun-chuan
YC
Zhu
Xiong-xiang
XX
Hu
Da-hai
DH
D000818:Animals; D002056:Burns / Q000097:blood*; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044967:Serum; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases