REGULATION OF HUMAN CARDIAC MYOSIN HEAVY-CHAIN GENES - THE EFFECT OF CATECHOLAMINE

The 5′-flanking regions of the α- and β-cardiac myosin heavy chain (MyHC) genes were excised from the cosmid human genomic clones using Hind III and Xbal for the α-MyHC gene, and the Hind III and Hind III sites for the β-MyHC gene. These fragments were linked to chloramphenicol acetyl transferase (CAT) vector to generate a chimeric fusion gene. These fusion genes were subsequently transfected to neonatal rat cardiac cultured cells to analyze the CAT activity. The α-MyHC gene is preferentially expressed as compared to the β-MyHC. In the presence of norepinephrine (NE) the β-MyHC gene is remarkably induced (within 24 hours following the addition of norepinephrine to the cardiocyte culture). However, the α-MyHC is also induced. Specific alpha andrenergic antagonists such as terazosin (Tz) partially suppressed both the α- and β-MyHC genes as revealed by the CAT activity. These findings suggest that catecholamine does activate the human cardiac MyHC genes but does not differentiate the specific expression of either the α- or β-MyHC genes. © 1992.