Effects of inhibition of mitochondrial protein synthesis in skeletal muscle.
To evaluate the participation of proteins derived from mitochondrial genes in the adaptive response of skeletal muscle to increased contractile activity, we administered chloramphenicol (CAP; 200-1,000 mg.kg-1.day-1), an inhibitor of translation from mitochondrial ribosomes, to adult rabbits undergoing electrical stimulation of the tibialis anterior muscle of one hind limb. In unmedicated animals, 10 days of electrical stimulation increased maximum velocity (Vmax) of cytochrome oxidase and citrate synthase by 214 +/- 17 and 201 +/- 16% (P less than 0.01). In a dose-dependent manner, CAP abolished activity-induced increases in cytochrome oxidase Vmax, suggesting that augmented mitochondrial protein synthesis is necessary for the adaptive response of enzymes that require protein subunits encoded by mitochondrial genes. However, CAP failed to inhibit activity-induced changes in Vmax of enzymes derived exclusively from nuclear genes (citrate synthase and aldolase). CAP also failed to inhibit activity-induced increases in mRNA transcribed from the nuclear genes encoding beta-F1 ATPase or myoglobin, or from the mitochondrial genes encoding 12S rRNA, 16S rRNA, or cytochrome b. These latter findings suggest that mitochondrial translation products do not participate in pretranslational regulation of these nuclear or mitochondrial genes in response to changes in contractile activity of skeletal muscle.
D000199:Actins / Q000235:genetics; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002701:Chloramphenicol / Q000494:pharmacology*; D003573:Cytochrome b Group / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005786:Gene Expression Regulation; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009119:Muscle Contraction; D009124:Muscle Proteins / Q000096:biosynthesis*; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism; D009211:Myoglobin / Q000096:biosynthesis; D006180:Proton-Translocating ATPases / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012335:RNA, Ribosomal / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D011817:Rabbits
D000199:Actins; D003573:Cytochrome b Group; D009124:Muscle Proteins; D009211:Myoglobin; D012333:RNA, Messenger; D012335:RNA, Ribosomal; D012336:RNA, Ribosomal, 16S; D002701:Chloramphenicol; D006180:Proton-Translocating ATPases