Leptin affects adenylate cyclase activity in H9c2 cardiac cell line: effects of short- and long-term exposure.
Leptin has been hypothesized to be a pathophysiologic link between obesity and cardiovascular diseases. Because the adenylate cyclase (AC) system is a main effector of beta-adrenergic receptors and leptin has been shown to modulate AC activity in other cell lines, a leptin impact on cardiac AC activity was hypothesized. Therefore, acute and chronic effects of leptin on a rat cardiac cell line (H9c2) were investigated. Leptin affected both basal (+ 13% at 30 min and -16.4% after 18 h v untreated cells) and catecholamine-stimulated AC activity (isoproterenol + leptin at 30 min or 18 h was +21% v untreated cells; norepinephrine + leptin at 30 min was +38.8% v untreated cells; and norepinephrine + leptin at 18 h was +6% v untreated cells). Thus, long-term leptin treatment was associated with a reduced AC activity and a different responsiveness to catecholamines. The AC activity on leptin treatment was accompanied by changes in levels of proteins structurally or functionally related to AC complex (AC, Gas, Gai, p21-ras). These data indicate that the AC complex is profoundly affected at more than one level by leptin treatment in the H9c2 cardiac cell line. Differences in AC activity after short- and long-term exposure to leptin and the interaction between leptin and catecholamine might provide further insight to the understanding of the development of hypertension and congestive heart failure in obese patients.
Department of Biochemistry, F. Cedrangolo, Second University of Naples, Italy. gennaro.illiano@unina2.it
Gennaro
G
Illiano
Silvio
S
Naviglio
Mario
M
Pagano
Annamaria
A
Spina
Emilio
E
Chiosi
Michelangela
M
Barbieri
Giuseppe
G
Paolisso
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D002460:Cell Line; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D020738:Leptin / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000201:enzymology*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats
D000316:Adrenergic alpha-Agonists; D002316:Cardiotonic Agents; D020738:Leptin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D009638:Norepinephrine