Abstract |
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.
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Authors | Chih-Yang Huang, Ling-Yang Hao, Dennis E Buetow |
Journal | Molecular and cellular biochemistry
(Mol Cell Biochem)
Vol. 231
Issue 1-2
Pg. 51-9
(Feb 2002)
ISSN: 0300-8177 [Print] Netherlands |
PMID | 11952165
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Calcium Channel Blockers
- Calcium Channels, L-Type
- Myosin Light Chains
- RNA, Messenger
- Troponin I
- myosin light chain 2
- Insulin-Like Growth Factor I
- Insulin-Like Growth Factor II
- Nicardipine
- Cardiac Myosins
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Topics |
- Animals
- Calcium Channel Blockers
(pharmacology)
- Calcium Channels, L-Type
(metabolism)
- Cardiac Myosins
(genetics, metabolism)
- Cardiomegaly
(chemically induced)
- Cell Size
(drug effects)
- Cells, Cultured
- Dose-Response Relationship, Drug
- Heart
(drug effects)
- Insulin-Like Growth Factor I
(pharmacology)
- Insulin-Like Growth Factor II
(pharmacology)
- Male
- Myosin Light Chains
(genetics, metabolism)
- Nicardipine
(pharmacology)
- RNA, Messenger
(genetics, metabolism)
- Rats
- Rats, Sprague-Dawley
- Troponin I
(genetics, metabolism)
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