Effects of losartan and PD123319 on antigensin II-induced proto-oncogene expression and protein synthesis in cultured neonatal rat cardiac myocytes.
To study the effects of specific angiotension II (Ang II) receptor, type-1 (AT1) antagonist (Losartan) and type-2 (AT2) antagonist (PD123319), on Ang II-induced proto-oncogene expression and synthesis of RNA and protein in neonatal rat cardiac myocytes, we used respectively [3H]-uridine and [3H]-leucine incorporation to measure the rate of RNA and protein synthesis, and analyzed the c-myc mRNA level by Northern blot. We found that an acceleration in the rate of RNA and protein synthesis was observed when exposed to 2.5 x 10(-6) mol.L-1 [Sar1] Ang II for 24 h (P < 0.01). Losartan inhibited the action in a dose-dependent manner. The level of c-myc mRNA was up-regulated to 340% of control by 2.5 x 10(-6) mol.L-1 Ang II, and Losartan (10(-5) mol.L-1) suppressed the increase of c-myc mRNA stimulated by Ang II. PD123319 showed similar inhibition on Ang II-induced RNA and protein synthesis, but did not inhibit c-myc expression. Thus, Ang II-stimulated expression of c-myc is mainly mediated by AT1 receptors, and contributes to cardiac myocyte hypertrophy while AT2 receptors are involved in mediation of cellular growth without altering of c-myc expression.
Ling
Q
Q
Laboratory of Molecular Pharmacology, Hunan Medical University, Changsha, China.
Guo
Z
Z
Chen
T
T
Yu
Y
Y
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000831:Animals, Newborn; D002455:Cell Division; D002478:Cells, Cultured; D015870:Gene Expression; D007093:Imidazoles / Q000494:pharmacology*; D019808:Losartan / Q000494:pharmacology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000235:genetics; D011725:Pyridines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D044140:Receptor, Angiotensin, Type 1
D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D016271:Proto-Oncogene Proteins c-myc; D011725:Pyridines; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; C073402:PD 123319; D019808:Losartan