Nuclear respiratory factor-2 subunit protein: Correlation with cytochrome oxydase and regulation by functional activity in the monkey primary visual cortex

Previous studies have shown that a transcription factor of the Ets family, nuclear respiratory factor 2 (NRF-2), can activate in vitro the gene expres sion of cytochrome oxidase (CO), a mitochondrial enzyme of oxidative metabo lism. The goals of our present study were to determine whether the distribu tion of NRF-2 alpha subunit proteins correlated with that of CO activity in the macaque monkey visual cortex and whether the level could be perturbed by visual deprivation. We generated polyclonal antibodies specifically agai nst human NRF-2 alpha subunit. Ln normal monkeys, patterns of NRF-2 alpha d istribution resembled closely that of CO activity: 1) NRF-2 alpha immunorea ctivity was localized in both nuclei and cytoplasm of neurons, but the leve ls differed among various laminae; 2) layers TVA, IVC, and VI, which had hi gh CO activity, were labeled more densely by NRF-2 alpha than layers I, IVE , and V, which contained lower levels of both NRF-2 alpha and CO activity; and 3) CO-rich puffs in layers II and III contained a higher level of NRF-2 alpha than CO-poor interpuffs. From 1 day to 7 days after monocular impuls e blockade with tetrodotoxin, there was a progressive reduction of NRF-2 al pha in deprived ocular dominance columns, in parallel with decreases in CO activity. These results suggest that local levels of NRF-2 in the monkey vi sual cortex closely reflect neuronal physiological and metabolic levels rev ealed by CO activity and that the expression of NRF-2 alpha, like that of C O, is regulated tightly by neural functional activity. (C) 1999 Wiley-Liss, Inc.