FAK-related nonkinase attenuates hypertrophy induced by angiotensin-II in cultured neonatal rat cardiac myocytes.

Abstract

AIM:

To examine the inhibitory effect of FAK-related nonkinase (FRNK) in cardiac hypertrophy in vitro and investigate the possible mechanisms.

METHODS:

A functional fragment of FRNK cDNA was amplified by reverse transcription-polymerase chain reaction and cloned into the vector pcDNA3.1. Hypertrophy in neonatal rat cardiac myocytes was established with angiotensin-II stimulation. The pcDNA3.1-FRNK or pcDNA3.1 was respectively transfected into cardiomyocytes by Lipofectamine 2000. The surface area and mRNA expression of atrial natriuretic peptide (ANP) of myocytes were employed to detect cardiac hypertrophy. NF-kappaB p65 protein in nuclear extracts, phosphorylation levels of ERK1/2 (p-ERK1/2) and AKT (p-AKT), as well as total ERK1/2, and AKT in variant treated cardiomyocytes were determined by Western blot.

RESULTS:

Under the stimulation of angiotensin II, the surface area of myocytes and levels of ANP mRNA were significantly increased. But transient transfection with pcDNA3.1-FRNK in advance may reduce the surface area and expression of ANP mRNA of hypertrophic myocytes. The protein levels of NF-kappaB p65 in nuclear extracts and p-ERK1/2, p-AKT in FRNK treated cardiomyocytes were significantly decreased compared with that in angiotensin-II induced cardiomyocytes, while different treatments had little effect on total ERK1/2 and AKT.

CONCLUSION:

FRNK may inhibit angiotensin-II-induced cardiomyocyte hypertrophy via decreasing phosphorylation levels at ERK1/2 and AKT, consequently downregulating nuclear translocation of NF-kappaB p65.

• Authors: Jin Qin, Zheng-xiang Liu
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 27 Issue 9 Pg. 1159-64 (Sep 2006) ISSN: 1671-4083 [Print] United States
• PMID: 16923336 (Publication Type: Journal Article)

Chemical References

• DNA, Complementary
• RNA, Messenger
• Transcription Factor RelA
• Angiotensin II
• Atrial Natriuretic Factor
• FAK-related nonkinase
• Protein-Tyrosine Kinases
• Proto-Oncogene Proteins c-akt
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3

Topics

• Angiotensin II (pharmacology)
• Animals
• Animals, Newborn
• Atrial Natriuretic Factor (biosynthesis, genetics)
• Cells, Cultured
• DNA, Complementary (genetics)
• Hypertrophy
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Myocytes, Cardiac (metabolism)
• Protein-Tyrosine Kinases (genetics, metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• RNA, Messenger (biosynthesis, genetics)
• Rats
• Rats, Sprague-Dawley
• Transcription Factor RelA (metabolism)
• Transfection