Muscle wasting and interleukin-6-induced atrogin-I expression in the cachectic Apc ( Min/+ ) mouse.
Interleukin-6 (IL-6) is necessary for cachexia in Apc ( Min/+ ) mice, but the mechanisms inducing this myofiber wasting have not been established. The purpose of this study was to examine gastrocnemius muscle wasting in the Apc ( Min/+ ) mouse and to determine IL-6 regulated mechanisms contributing to muscle loss. Gastrocnemius type IIB mean fiber cross-sectional area (CSA) from Apc ( Min/+ ) mice decreased 32% between 13 and 22 weeks of age. Apc ( Min/+ ) mice lacking IL-6 did not have type IIB fiber atrophy, while overexpression of circulating IL-6 exacerbated the loss of type IIB fiber CSA in Apc ( Min/+ ) mice. Muscle Atrogin-I mRNA expression was induced at least ninefold at 18 and 22 weeks of age compared to 13-week-old mice. Atrogin-I gene expression was also induced by overexpression of circulating IL-6. These data suggest that high circulating IL-6 levels induce type IIB fiber CSA loss in Apc ( Min/+ ) mice, and circulating IL-6 is sufficient to regulate Atrogin-I gene expression in cachectic mice.
Baltgalvis
Kristen A
KA
Exercise Science Department, University of South Carolina, Columbia, USA.
Berger
Franklin G
FG
Peña
Maria Marjorette O
MM
Davis
J Mark
JM
White
James P
JP
Carson
James A
JA
D000818:Animals; D002100:Cachexia / Q000473:pathology / Q000503:physiopathology*; D015870:Gene Expression; D015850:Interleukin-6 / Q000097:blood / Q000502:physiology*; D007417:Intestinal Polyps / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000378:metabolism; D053580:Muscle Strength / Q000502:physiology; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D009133:Muscular Atrophy / Q000473:pathology / Q000503:physiopathology*; D009210:Myofibrils / Q000473:pathology; D044843:SKP Cullin F-Box Protein Ligases / Q000096:biosynthesis*
D015850:Interleukin-6; D009124:Muscle Proteins; C413644:Rnf30 protein, mouse; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases