[CaN-NFAT3 signal pathway: a crucial hinge relates Ca2+ signal with cardiomyocyte hypertrophy].
OBJECTIVE
To investigate the role of [Ca2+]i from different origins in the course of myocardial hypertrophy mediated by CaN-NFAT3 signal transduction.


METHODS
The primarily cultured cardiomyocyte were irritated with angiotensin (Ang) II and ryanodine (RY) which cause Ca2+ inflow and release respectively. Then to observe the changes of CaN-NFAT3 pathway were then observed. Western blotting was employed to semi-quantify CaN, NFAT3 and GATA4. The distribution of NFAT3 was shown with immunocytochemistry, (3)H-Leu incorporation was used as an index of myocyte hypertrophy. Cyclosporin A (CsA) was applied to restrain CaN-NFAT3 pathway as a kind of CaN-selective antagonist.


RESULTS
CaN, NFAT3, GATA4 expression significantly increased 1 and 3 days after the stimulation of cardiomyocytes with Ang II and RY (10(-7) mol/L) as compared with that of a control group (P > 0.05) and (3)H-Leu incorporation distinctly increased after Ang II and RY (10(-7) mol/L) stimulation (P > 0.05 versus control group). On the first day of Ang II and RY stimulation, NFAT3 was shown mainly as intra-nuclear expression rather than cytoplasmic expression as seen in the control group. All of the above effects were suppressed by CsA administration, but they were rarely suppressed if CsA was not administered (P > 0.05).


CONCLUSIONS
It is shown that both Ca2+ inflow and release may activate CaN-NFAT3 signal pathway, which responds to increase of [Ca2+]i and is independent of its origin, indicating the augment of [Ca2+]i may trigger CaN-NFAT3 signal transduction and consequently induce myocyte hypertrophy. Moreover, CsA may restrain the expression and activation of CaN-NFAT3 and protein synthesis of myocytes in response to Ang II and RY stimulation.
Department of Cardiology, Xinqiao Hospital, the Third Military Medical University; Chongqing 400037, China. 19321224@mail.tmmu.com.cn
Shan-jun
SJ
Zhu
Yong-jian
YJ
Yang
Lin-jun
LJ
Yu
Lan
L
Huang
D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000378:metabolism*; D002312:Cardiomyopathy, Hypertrophic / Q000378:metabolism / Q000503:physiopathology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050991:GATA4 Transcription Factor; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010446:Peptide Fragments / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010446:Peptide Fragments; D014157:Transcription Factors; C104454:angiotensin II (1-8); D000804:Angiotensin II; D002154:Calpain; D002118:Calcium