Fu W, Killen M, Culmsee C, Dhar S, Pandita T K, Mattson M P
Sanders Brown Research Center on Aging, University of Kentucky, Lexington 40536, USA.
J Mol Neurosci. 2000 Feb-Apr;14(1-2):3-15. doi: 10.1385/JMN:14:1-2:003.
Telomerase, a specialized reverse transcriptase (RT) linked to cell immortalization and cancer, has been thought not to be expressed in postmitotic cells. We now report that telomerase activity and its essential catalytic subunit, telomerase reverse transcriptase (TERT), are expressed in neurons in the brains of rodents during embryonic and early postnatal development, and are subsequently downregulated. Suppression of TERT expression in cultured embryonic hippocampal neurons increases their vulnerability to apoptosis and excitotoxicity. Overexpression of TERT in PC12 cells suppresses apoptosis induced by trophic factor withdrawal. TERT exerts its anti-apoptotic action at an early stage of the cell death process prior to mitochondrial dysfunction and caspase activation. TERT may serve a neuron survival-promoting function in the developing brain, and downregulation of TERT in the adult brain may contribute to increased neuronal vulnerability in various age-related neurodegenerative disorders.
端粒酶是一种与细胞永生化和癌症相关的特殊逆转录酶(RT),一直被认为在有丝分裂后细胞中不表达。我们现在报告,在胚胎期和出生后早期发育阶段,啮齿动物大脑中的神经元表达端粒酶活性及其必需的催化亚基端粒酶逆转录酶(TERT),随后其表达下调。在培养的胚胎海马神经元中抑制TERT表达会增加它们对凋亡和兴奋毒性的易感性。在PC12细胞中过表达TERT可抑制因营养因子撤除诱导的凋亡。TERT在细胞死亡过程的早期,在线粒体功能障碍和半胱天冬酶激活之前发挥其抗凋亡作用。TERT可能在发育中的大脑中发挥促进神经元存活的功能,而成人大脑中TERT的下调可能导致各种与年龄相关的神经退行性疾病中神经元易感性增加。