Search Results
Search for other papers by D Dardevet in
Google Scholar
PubMed
Search for other papers by C Sornet in
Google Scholar
PubMed
Search for other papers by I Savary in
Google Scholar
PubMed
Search for other papers by E Debras in
Google Scholar
PubMed
Search for other papers by P Patureau-Mirand in
Google Scholar
PubMed
Search for other papers by J Grizard in
Google Scholar
PubMed
This study was performed to assess the effect of glucocorticoids (dexamethasone) on insulin- and IGF-I-regulated muscle protein metabolism in adult and old rats. Muscle atrophy occurred more rapidly in old rats, and recovery of muscle mass was impaired when compared with adults. Muscle wasting resulted mainly from increased protein breakdown in adult rat but from depressed protein synthesis in the aged animal. Glucocorticoid treatment significantly decreased the stimulatory effect of insulin and IGF-I on muscle protein synthesis in adult rats by 25.9 and 58.1% respectively. In old rats, this effect was even greater, being 49.3 and 100% respectively. With regard to muscle proteolysis, glucocorticoids blunted the anti-proteolytic action of insulin and IGF-I in both age groups. During the recovery period, adult rats reversed the glucocorticoid-induced resistance of muscle protein metabolism within 3 days, at which time old rats still exhibited the decrease in insulin-regulated proteolysis. In conclusion, the higher sensitivity of old rat muscle to glucocorticoids may in part result from the greater modification of the effects of insulin and IGF-I on muscle protein metabolism. These responses to glucocorticoids in old rats may be associated with the emergence of muscle atrophy with advancing age.
Search for other papers by Z Hochberg in
Google Scholar
PubMed
Search for other papers by T Amit in
Google Scholar
PubMed
Search for other papers by A Flyvbjerg in
Google Scholar
PubMed
Search for other papers by I Dørup in
Google Scholar
PubMed
Abstract
Potassium (K+) deficiency is associated with growth retardation in both man and experimental animals. Growth hormone (GH) administration to such animals prevents, to some extent, weight loss and selective muscle atrophy, but does not affect tail and tibia length even with supraphysiological doses. The present study was undertaken to investigate the possible effect of K+ deficiency on the hepatic GH receptor and GH-binding protein (BP). Young female Wistar rats were maintained on K+-deficient fodder and distilled water, and compared with pair-fed and ad-libitumfed control groups. After 15 days GH-BP and electrolytes were measured in sera, GH receptors were studied in liver membranes by 125I-labeled human GH binding and muscles were weighed and saved for electrolyte measurements. K+-deficient rats showed complete growth arrest compared with an intermediate weight gain of the pair-fed group. Serum K+ was very low, at 1·5 ±0·1 mmol/l, compared with the mean value of 5·3 mmol/l of control animals. Somatogenic and lactogenic receptors in liver membranes and serum GH-BP levels were significantly (P<0·05) lower in K+ deficiency, as compared with their pair-fed controls. Liver GH receptors correlated significantly (P<0·05) with serum GH-BP levels. The growth variables correlated positively with both hepatic somatogenic and lactogenic receptors and serum GH-BP levels, with correlation coefficients that were highest against serum GH-BP and lowest against liver lactogenic receptors. Serum and muscle K+ correlated significantly (P<0·05) with both liver GH receptors and serum GH-BP, with correlation coefficients that were higher against serum GH-BP. Lactogenic receptors had a lower or no correlation. It is concluded that GH receptor deficiency may be involved in the growth retardation of K+ deficiency.
Journal of Endocrinology (1995) 147, 253–258
Search for other papers by R Lalani in
Google Scholar
PubMed
Search for other papers by S Bhasin in
Google Scholar
PubMed
Search for other papers by F Byhower in
Google Scholar
PubMed
Search for other papers by R Tarnuzzer in
Google Scholar
PubMed
Search for other papers by M Grant in
Google Scholar
PubMed
Search for other papers by R Shen in
Google Scholar
PubMed
Search for other papers by S Asa in
Google Scholar
PubMed
Search for other papers by S Ezzat in
Google Scholar
PubMed
Search for other papers by NF Gonzalez-Cadavid in
Google Scholar
PubMed
The mechanism of the loss of skeletal muscle mass that occurs during spaceflight is not well understood. Myostatin has been proposed as a negative modulator of muscle mass, and IGF-I and IGF-II are known positive regulators of muscle differentiation and growth. We investigated whether muscle loss associated with spaceflight is accompanied by increased levels of myostatin and a reduction in IGF-I and -II levels in the muscle, and whether these changes correlate with an increase in muscle proteolysis and apoptosis. Twelve male adult rats sent on the 17-day NASA STS-90 NeuroLab space flight were divided upon return to earth into two groups, and killed either 1 day later (R1) or after 13 days of acclimatization (R13). Ground-based control rats were maintained for the same periods in either vivarium (R3 and R15, respectively), or flight-simulated cages (R5 and R17, respectively). RNA and protein were isolated from the tibialis anterior, biceps femoris, quadriceps, and gastrocnemius muscles. Myostatin, IGF-I, IGF-II and proteasome 2c mRNA concentrations were determined by reverse transcription/PCR; myostatin and ubiquitin mRNA were also measured by Northern blot analysis; myostatin protein was estimated by immunohistochemistry; the apoptotic index and the release of 3-methylhistidine were determined respectively by the TUNEL assay and by HPLC. Muscle weights were 19-24% lower in the R1 rats compared with the control R3 and R5 rats, but were not significantly different after the recovery period. The myostatin/beta-actin mRNA ratios (means+/-s.e.m. ) were higher in the muscles of the R1 rats compared with the control R5 rats: 5.0-fold in tibialis (5.35 +/- 1.85 vs 1.07 +/- 0.26), 3.0-fold in biceps (2.46+/-0.70 vs 0.81 +/- 0.04), 1.9-fold in quadriceps (7.84 +/- 1.73 vs 4.08 +/- 0.52), and 2.2-fold in gastrocnemius (0.99 +/- 0.35 vs 0.44 +/- 0.17). These values also normalized upon acclimatization. Our antibody against a myostatin peptide was validated by detection of the recombinant human myostatin protein on Western blots, which also showed that myostatin immunostaining was increased in muscle sections from R1 rats, compared with control R3 rats, and normalized upon acclimatization. In contrast, IGF-II mRNA concentrations in the muscles from R1 rats were 64-89% lower than those in R3 animals. With the exception of the gastrocnemius, IGF-II was also decreased in R5 animals maintained in flight-simulated cages, and normalized upon acclimatization. The intramuscular IGF-I mRNA levels were not significantly different between the spaceflight rats and the controls. No increase was found in the proteolysis markers 3-methyl histidine, ubiquitin mRNA, and proteasome 2C mRNA. In conclusion, the loss of skeletal muscle mass that occurs during spaceflight is associated with increased myostatin mRNA and protein levels in the skeletal muscle, and a decrease in IGF-II mRNA levels. These alterations are normalized upon restoration of normal gravity and caging conditions. These data suggest that reciprocal changes in the expression of myostatin and IGF-II may contribute to the multifactorial pathophysiology of muscle atrophy that occurs during spaceflight.
Department of Anatomy, Department of Medicine, Integrated Metabolomics Research Group, Department of Life Science, Korea University College of Medicine, Seoul 136-701, South Korea
Search for other papers by Nami Kim in
Google Scholar
PubMed
Search for other papers by Jung Ok Lee in
Google Scholar
PubMed
Search for other papers by Hye Jeong Lee in
Google Scholar
PubMed
Search for other papers by Yong Woo Lee in
Google Scholar
PubMed
Search for other papers by Hyung Ip Kim in
Google Scholar
PubMed
Search for other papers by Su Jin Kim in
Google Scholar
PubMed
Search for other papers by Sun Hwa Park in
Google Scholar
PubMed
Search for other papers by Chul Su Lee in
Google Scholar
PubMed
Search for other papers by Sun Woo Ryoo in
Google Scholar
PubMed
Department of Anatomy, Department of Medicine, Integrated Metabolomics Research Group, Department of Life Science, Korea University College of Medicine, Seoul 136-701, South Korea
Search for other papers by Geum-Sook Hwang in
Google Scholar
PubMed
Search for other papers by Hyeon Soo Kim in
Google Scholar
PubMed
to a more stable form. It was demonstrated that intracellular calcium signalling is associated with skeletal muscle atrophy ( Zhou et al . 2010 , Mirza & Tisdale, 2012 ). In this study, isoeugenol increased the intracellular calcium of skeletal C2C
Search for other papers by Maria Carolina S Mendes in
Google Scholar
PubMed
Search for other papers by Gustavo D Pimentel in
Google Scholar
PubMed
Search for other papers by Felipe O Costa in
Google Scholar
PubMed
Search for other papers by José B C Carvalheira in
Google Scholar
PubMed
expenditure during periods of caloric intake restriction ( Hart 1988 , Saper & Breder 1992 , 1994 ). Molecular mechanisms of skeletal muscle wasting Cachexia-induced muscle atrophy occurs as a result of both reduced protein synthesis at initiation and
Search for other papers by Lingyun Lu in
Google Scholar
PubMed
Search for other papers by Li Tian in
Google Scholar
PubMed
-Leheudre 2022 ). Muscle weight and strength decrease in menopausal women, which indicates that a reduction in estrogen and its receptors can cause muscle loss and muscle atrophy ( Buckinx & Aubertin-Leheudre 2022 ). Maintaining skeletal muscle function is
Search for other papers by Soo Yeon Jang in
Google Scholar
PubMed
Search for other papers by Kyung Mook Choi in
Google Scholar
PubMed
macrophage phenotype in vitro and in vivo ( Bouredji et al. 2021 ). Genetic deletion of OPG demonstrated increased circulating RANKL levels, leading to osteoporosis and muscle atrophy. Treatment with anti-RANKL significantly restored muscle strength and
Search for other papers by Estíbaliz Castillero in
Google Scholar
PubMed
Search for other papers by María López-Menduiña in
Google Scholar
PubMed
Search for other papers by Ana Isabel Martín in
Google Scholar
PubMed
Search for other papers by María Ángeles Villanúa in
Google Scholar
PubMed
Search for other papers by Asunción López-Calderón in
Google Scholar
PubMed
, and rheumatoid arthritis. Cachexia can also induce a decrease in body weight that is associated with muscle atrophy and sometimes with fat mass depletion. The increased release of cytokines and other proinflammatory mediators plays a crucial role in
Research Fellow of Japan Society for Promotion Science, Chiyoda-ku, Tokyo, Japan
Department of Human Sciences, Kanagawa University, Rokkakubashi, Kanagawa-ku, Yokohama-shi, Kanagawa, Japan
Search for other papers by Takanaga Shirai in
Google Scholar
PubMed
Search for other papers by Tomohiro Iwata in
Google Scholar
PubMed
Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennodai, Tsukuba, Ibaraki, Japan
Search for other papers by Kazuki Uemichi in
Google Scholar
PubMed
Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennodai, Tsukuba, Ibaraki, Japan
Search for other papers by Riku Tanimura in
Google Scholar
PubMed
Search for other papers by Ryoto Iwai in
Google Scholar
PubMed
Search for other papers by Tohru Takemasa in
Google Scholar
PubMed
( Katsimpardi et al. 2020 ). These factors, which are influenced by CR, may play a pivotal role in preserving skeletal muscle mass and, therefore, could serve as target molecules to prevent muscle atrophy. We hypothesized that during CR, the skeletal muscle
Search for other papers by Mark E Cleasby in
Google Scholar
PubMed
Search for other papers by Pauline M Jamieson in
Google Scholar
PubMed
Search for other papers by Philip J Atherton in
Google Scholar
PubMed
. Dotted arrows indicate likely causative relationships and suggest that IR may be central to the syndrome. Although numerous animal models have been established to study muscle atrophy associated with disuse ( Bodine et al. 2001 a ), denervation
