Viral expression of insulin-like growth factor-I isoforms promotes different responses in skeletal muscle

被引:91
作者
Barton, ER
机构
[1] Univ Penn, Dept Anat & Cell Biol, Sch Dent Med, Philadelphia, PA 19104 USA
[2] Univ Penn, Penn Muscle Inst, Philadelphia, PA 19104 USA
关键词
adeno-associated virus; E peptide; IGF-I splicing;
D O I
10.1152/japplphysiol.01405.2005
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Insulin-like growth factor I (IGF-I) is a critical protein for skeletal muscle development and regeneration. Its ability to promote skeletal muscle hypertrophy has been demonstrated by several methods. Alternative splicing of the Igf-1 gene does not affect the mature IGF-I protein but does produce different E peptide extensions, which have been reported to modify the potency of IGF-I. Viral-mediated delivery of murine IGF-IA and IGF-IB into skeletal muscle of 2-wk-old and 6-mo-old mice was utilized to compare the effects of the isoforms on muscle mass. In young mice, tissue content of IGF-I protein was significantly higher in rAAV-treated muscles than control muscles at 1, 2, and 4 mo postin-jection. Viral injection of IGF-IB produced two- to sevenfold more IGF-I than rAAVIGF-IA. Hypertrophy was observed 2 and 4 mo postinjection, where both rAAVIGF-IA and rAAVIGF-IB were equally effective in increasing muscle mass. These results suggest that there is a threshold of IGF-I production necessary to promote muscle hypertrophy in young growing animals regardless of isoform. In 6-mo-old animals, only rAAVIGF-IA produced significant increases in muscle size, even though increased IGF-I content was observed after injection of both isoforms. Therefore, the ability for IGF-IB to promote muscle hypertrophy is only effective in growing animals, suggesting that the bioavailability of this isoform or its receptor affinity diminishes with age.
引用
收藏
页码:1778 / 1784
页数:7
相关论文
共 32 条
[11]   The mitogenic and myogenic actions of insulin-like growth factors utilize distinct signaling pathways [J].
Coolican, SA ;
Samuel, DS ;
Ewton, DZ ;
McWade, FJ ;
Florini, JR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (10) :6653-6662
[12]   TISSUE CONCENTRATIONS OF SOMATOMEDIN-C - FURTHER EVIDENCE FOR MULTIPLE SITES OF SYNTHESIS AND PARACRINE OR AUTOCRINE MECHANISMS OF ACTION [J].
DERCOLE, AJ ;
STILES, AD ;
UNDERWOOD, LE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1984, 81 (03) :935-939
[13]   A MUSCLE-SPECIFIC ENHANCER IS LOCATED AT THE 3' END OF THE MYOSIN LIGHT-CHAIN 1/3 GENE LOCUS [J].
DONOGHUE, M ;
ERNST, H ;
WENTWORTH, B ;
NADALGINARD, B ;
ROSENTHAL, N .
GENES & DEVELOPMENT, 1988, 2 (12B) :1779-1790
[14]  
FOYT HL, 1991, J BIOL CHEM, V266, P7300
[15]   EFFECT OF GROWTH-HORMONE ON LEVELS OF DIFFERENTIALLY PROCESSED INSULIN-LIKE GROWTH FACTOR-I MESSENGER-RNAS IN TOTAL AND POLYSOMAL MESSENGER-RNA POPULATIONS [J].
FOYT, HL ;
LANAU, F ;
WOLOSCHAK, M ;
LEROITH, D ;
ROBERTS, CT .
MOLECULAR ENDOCRINOLOGY, 1992, 6 (11) :1881-1888
[16]   Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy [J].
Gao, GP ;
Alvira, MR ;
Wang, LL ;
Calcedo, R ;
Johnston, J ;
Wilson, JM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (18) :11854-11859
[17]   Cloning of local growth factors involved in the determination of muscle mass [J].
Goldspink, G .
BRITISH JOURNAL OF SPORTS MEDICINE, 2000, 34 (03) :159-160
[18]   Mechanical signals, IGF-I gene splicing, and muscle adaptation [J].
Goldspink, G .
PHYSIOLOGY, 2005, 20 :232-238
[19]   Expression of IGF-I splice variants in young and old human skeletal muscle after high resistance exercise [J].
Hameed, M ;
Orrell, RW ;
Cobbold, M ;
Goldspink, G ;
Harridge, SDR .
JOURNAL OF PHYSIOLOGY-LONDON, 2003, 547 (01) :247-254
[20]   Viral expression of insulin-like growth factor-I enhances muscle hypertrophy in resistance-trained rats [J].
Lee, S ;
Barton, ER ;
Sweeney, HL ;
Farrar, RP .
JOURNAL OF APPLIED PHYSIOLOGY, 2004, 96 (03) :1097-1104