Insulin-like growth factor-induced hypertrophy of cultured adult rat cardiomyocytes is L-type calcium-channel-dependent.
The insulin-like growth factors-I and -II are potent growth stimulators in vivo and for many different cultured cells in vitro. Here IGF-I and -II are shown to directly induce hypertrophy of adult rat ventricular cardiomyocytes in serum-free medium as demonstrated by their increased size, total protein synthesis, and transcription of muscle-specific genes. The cells hypertrophied within 1 day when exposed to as little as 10(-11) M IGF-I or 10(-10) M IGF-II. With 10(-8) M IGF-I, cell size was significantly increased 34% by 1 day of culture and 57% by 2 days. With 10(-8) M IGF-II, cell size was similarly increased 32% by day 1 and 57% by 2 days. During hypertrophy, total protein synthesis was increased 2.3-fold with IGF-I and 2-fold with IGF-II. Gene expression for myosin light chain 2 and troponin I was upregulated with either growth factor. Hypertrophy induced by IGF-I was blocked by IGF binding protein-3, which binds IGF-I, while that induced by IGF-II was blocked by antibodies against IGF-II. Nicardipine, an inhibitor of L-type Ca2+-channels, completely blocked the hypertrophy induced by either IGF showing for the first time that such voltage-dependent channels are necessary for the hypertrophic effects of the IGFs on adult cardiomyocytes.
Huang
Chih-Yang
CY
Department of Molecular and Integrative Physiology, University of Illinois, Urbana 61801, USA.
Hao
Ling-Yang
LY
Buetow
Dennis E
DE
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D024722:Cardiac Myosins / Q000235:genetics / Q000378:metabolism; D006332:Cardiomegaly / Q000139:chemically induced*; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D008297:Male; D018994:Myosin Light Chains / Q000235:genetics / Q000378:metabolism; D009529:Nicardipine / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019210:Troponin I / Q000235:genetics / Q000378:metabolism
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D018994:Myosin Light Chains; D012333:RNA, Messenger; D019210:Troponin I; C107184:myosin light chain 2; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D009529:Nicardipine; D024722:Cardiac Myosins