Altered gene expression in steroid-treated denervated muscle.
In rats treated with high-dose corticosteroids, skeletal muscle that is denervated in vivo (steroid-denervated) develops electrical inexcitability similar to that seen in patients with acute quadriplegic myopathy. To determine whether changes in muscle gene transcription might underlie inexcitability of steroid-denervated muscle we performed RNase protection assays to quantitate adult (SkM1) and embryonic (SkM2) sodium channel isoforms and chloride channel (CLC-1) mRNA levels in control, denervated, steroid-innervated, and steroid-denervated skeletal muscle. While SkM1 mRNA levels were relatively unaffected by denervation or steroid treatment, SkM2 mRNA levels were increased by both. These effects were synergistic and high levels of SkM2 mRNA were expressed in denervated muscle exposed to corticosteroids. Skeletal muscle CLC-1 mRNA levels were decreased by denervation. To better understand the marked upregulation of SkM2 in steroid-denervated muscle we examined changes in myogenin and glucocorticoid receptor mRNA levels. However, changes in these mRNA levels cannot account for the upregulation of SkM2 in steroid-denervated muscle.
Rich
M M
MM
Department of Neurology, Emory University School of Medicine, WMB Suite 6000, 1639 Pierce Drive, Atlanta, GA 30322, USA. mmrich@emory.edu
Kraner
S D
SD
Barchi
R L
RL
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000009:adverse effects* / Q000627:therapeutic use; D000818:Animals; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism; D003714:Denervation / Q000009:adverse effects*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000294:innervation* / Q000503:physiopathology; D018008:Myogenin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics
D000305:Adrenal Cortex Hormones; C086321:CLC-1 channel; D018118:Chloride Channels; C503799:MYOG protein, human; C503803:Myog protein, rat; D018008:Myogenin; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D015222:Sodium Channels