GATA4-mediated cardiac hypertrophy induced by d-myo-inositol 1,4,5-tris-phosphate.
We evaluated the effects of d-myo-inositol 1,4,5-tris-phosphate on cardiac hypertrophy. d-myo-inositol 1,4,5-tris-phosphate augmented cardiac hypertrophy as evidenced by its effects on DNA synthesis, protein synthesis, and expression of immediate-early genes c-myc and c-fos, beta-myosin heavy chain, and alpha-actin. The administration of d-myo-inositol 1,4,5-tris-phosphate increased the expression of nuclear factor of activated T-cells and cardiac-restricted zinc finger transcription factor (GATA4). Real-time quantitative RT-PCR showed that d-myo-inositol 1,4,5-tris-phosphate-induced GATA4 mRNA was significantly enhanced even in the presence of the calcineurin inhibitor, cyclosporine A. The effect of d-myo-inositol 1,4,5-tris-phosphate was blocked after inhibition of inositol-trisphosphate receptors but not after inhibition of c-Raf/mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (ERK) or p38 mitogen-activated protein kinase pathways. The study shows that d-myo-inositol 1,4,5-tris-phosphate-induced cardiac hypertrophy is mediated by GATA4 but independent from the calcineurin pathway.
Zhu
Zhiming
Z
Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing Hypertension Institute, Chongqing, PR China. zhuzming@mail.dph-fsi.com
Zhu
Shanjun
S
Liu
Daoyan
D
Yu
Zengping
Z
Yang
Yongjian
Y
van der Giet
Markus
M
Tepel
Martin
M
D000818:Animals; D000831:Animals, Newborn; D006332:Cardiomegaly / Q000139:chemically induced* / Q000378:metabolism*; D002478:Cells, Cultured; D050991:GATA4 Transcription Factor / Q000378:metabolism*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015544:Inositol 1,4,5-Trisphosphate / Q000009:adverse effects*; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D050991:GATA4 Transcription Factor; C084365:Gata4 protein, rat; D015544:Inositol 1,4,5-Trisphosphate