title: Neural control of gene expression in skeletal muscle. Effects of chronic stimulation on lactate dehydrogenase isoenzymes and citrate synthase.
abstract: The aim of this study was to investigate the effects of neural activity on the expression of fibre-type-specific patterns of metabolic enzymes at the levels of transcription and translation. For this purpose, changes in tissue amounts of citrate synthase (CS) and the H- and M-subunits of lactate dehydrogenase (LDH) were followed in fast-twitch rabbit muscles during low-frequency (10 Hz, 12 h/day) nerve stimulation. These stimulation-induced alterations were correlated with changes in tissue amounts of the total poly(A)+ (polyadenylated) RNA, poly(A)+ RNAs specifically translatable in vitro, yield of total ribosomes and distributions of monosomes and polysomes. The tissue contents of poly(A)+ RNAs translatable in vitro coding for CS and H- and M-LDH were quantified by immunoprecipitation of their translation products. Increases in total ribosome yields occurred after 4 days' stimulation, reaching a maximum between 14 and 21 days. Stimulation for only 1-2 days greatly increased the amount of monosomes. An increase in polysomes occurred before that in total ribosomes, suggesting that monosomes were integrated into polysomes. Total poly(A)+ RNA significantly increased in muscles stimulated for more than 6 days. A maximum increase of 2.5-fold was attained after 14-21 days. Chronic stimulation progressively induced the appearance of LDH isoenzymes containing the H-subunit, with a predominance of LDH-3. This shift corresponded to a slow decay of the M-subunit and a 2-fold steep increase in the H-subunit. These changes correlated with those of the respective poly(A)+ RNAs translatable in vitro, thus indicating that the re-arrangement of the LDH isoenzyme pattern is mainly due to qualitatively and quantitatively altered transcription. The increase in CS was biphasic and consisted of a moderate rise during the first 4 days of stimulation and a steep rise thereafter. The latter coincided with a steep increase in poly(A)+ RNA translatable in vitro coding for CS. In view of the early increase in translational capacity, it was concluded that the initial rise in CS resulted from selective post-transcriptional control and enhanced translation in vivo of existing mRNA, whereas its steep increase was due to enhanced transcription. These results indicate that the neurally regulated expression of phenotype-specific properties in muscle includes control of both transcription and translation.
mesh_terms: D000818:Animals; D002950:Citrate (si)-Synthase / Q000235:genetics*; D004558:Electric Stimulation; D005786:Gene Expression Regulation; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase / Q000235:genetics*; D008297:Male; D009132:Muscles / Q000201:enzymology / Q000294:innervation*; D007652:Oxo-Acid-Lyases / Q000235:genetics*; D011061:Poly A / Q000235:genetics; D014176:Protein Biosynthesis; D012313:RNA / Q000235:genetics; D012333:RNA, Messenger; D011817:Rabbits; D012270:Ribosomes / Q000502:physiology; D009435:Synaptic Transmission; D014158:Transcription, Genetic
chemical_list: D007527:Isoenzymes; D012333:RNA, Messenger; D011061:Poly A; D012313:RNA; D007770:L-Lactate Dehydrogenase; D002950:Citrate (si)-Synthase; D007652:Oxo-Acid-Lyases