Sarkander H I, Knoll-Köhler E, Cervos-Navarro J
J Pharmacol Exp Ther. 1978 May;205(2):503-14.
Administration of 6-aminonicotinamide (6-AN) to rats leads to an opposite effect on the rate at which [3H]UMP is incorporated in vitro into nuclear cerebral neuronal and glial RNA. The inhibition of glial RNA synthesis is temporarily accompanied by both a reduction of the number of RNA initiation sites on glial chromatin and a reduction of [3H]acetate uptake into glial chromatin-bound histones mainly as regards the fraction H2B, H3 and H4. The slight stimulation of neuronal RNA synthesis 6 hours after 6-AN seemed to be caused exclusively by a less steric restriction of neuronal chromatin, whereas the more pronounced stimulation at 24 hours may be related to both a higher activity and/or amount of endogenous neuronal RNA polymerases and an increase in the total number of RNA initiation sites present on the neuronal chromatin. The increase in the total number of neuronal RNA initiation sites is closely parallel with a higher degree of acetylation of neuronal chromatin-bound histone fractions. The 6-AN-induced variations of glial and neuronal in vitro RNA synthesis are discussed in correlation with the neurotoxic action of 6-AN in vivo.
给大鼠注射6-氨基烟酰胺（6-AN）会对体外[3H]UMP掺入细胞核脑神经元和神经胶质RNA的速率产生相反的影响。神经胶质RNA合成的抑制暂时伴随着神经胶质染色质上RNA起始位点数量的减少以及[3H]乙酸盐掺入神经胶质染色质结合组蛋白的减少，主要涉及H2B、H3和H4组分。6-AN注射6小时后神经元RNA合成的轻微刺激似乎完全是由神经元染色质空间位阻的减小引起的，而24小时时更明显的刺激可能与内源性神经元RNA聚合酶的活性和/或数量增加以及神经元染色质上RNA起始位点总数的增加有关。神经元RNA起始位点总数的增加与神经元染色质结合组蛋白组分乙酰化程度的提高密切平行。讨论了6-AN诱导的神经胶质和神经元体外RNA合成变化与6-AN体内神经毒性作用的相关性。
