Differential Effect of Denervation on Free‐Radical Scavenging Enzymes in Slow and Fast Muscle of Rat

Abstract

: To determine the effect of denervation on the free‐radical scavenging systems in relation to the mitochondrial oxidative metabolism in the slow‐twitch soleus and fast‐twitch extensor digitomm longus (EDL) muscles, the sciatic nerve of the rat was crushed in the mid‐thigh region and the muscle tissue levels of five enzymes were studied 2 and 5 weeks following crush. Recently developed radioimmunoassays were utilized for the selective measurement of cuprozinc (cytosolic) and man‐gano (mitochondrial) superoxide dismutases. Total tissue content of cuprozinc superoxide dismutase showed a mild decrease after denervation in slow but not in fast muscle. Manganosuperoxide dismutase and fumarase decreased markedly at 2 weeks and returned toward control levels by 5 weeks, the changes appearing to be greater in slow than in fast muscle. At 2 weeks, cytochrome c oxidase decreased significantly in slow, but not in fast muscle. GSH‐peroxidase at baseline was 10‐fold higher in slow than in fast muscle, markedly decreased at 2 weeks in slow muscle, and returned toward control levels at 5 weeks, whereas the total enzyme activity in fast muscle did not change through 5 weeks. These data represent the first systematic report of free radical scavenging systems in slow and fast muscles in response to denervation. Selective modification of cuprozinc and manganosuper‐oxide dismutases and differential regulation of GSH‐peroxidase was demonstrated in slow and fast muscle.

C/EBPα is a major activator for the transcription of rat Cu/Zn superoxide dismutase gene in liver cell

“…In particular kidney and liver show the highest Cu/Zn SOD mRNA levels [6]. This distribution is consistent with the relative protein concentration and activity of SOD1 in these tissues [7]. There are four known major factor families expressed in the liver: C/EBP (CCAAT/enhancer-binding protein), HNF-1, HNF-3 and HNF-4 [8].…”

Positive and negative regulatory elements in the upstream region of the rat Cu/Zn-superoxide dismutase gene

“…It is known that SOD1 is expressed at high levels in liver, and its distribution is consistent with the relative protein concentration and activity of SOD [47]. These observations provided the relationship between the tissue distribution of SOD1 and the role of tissue-specific transcription factors.…”

Immunohistochemical localization of copper-zinc and manganese superoxide dismutases in rat tissues.

“…Likewise, the two isoenzymes may play a different physiological role from each other . We previously demonstrated that the tissue distribution of immunoreactive CuZnSOD in rat organs was quite different from that of MnSOD (2), and that the physiological regulation of the latter was independent of that of the former (3,4).…”