Neuroprotective signaling mechanisms of telomerase in neuronal cells against oxidative stress

Abstract

Canonically, telomerase was viewed as an enzyme with only one action: maintenance and extension of telomeres to prevent cellular senescence/aging. Novel roles for telomerase, particularly its catalytic subunit telomerase reverse transcriptase (TERT), in normal brain function and protection of CNS cells have recently emerged. However, little is known about whether telomerase also exerts neuroprotective effects in neuronal cells against oxidative stress and how its activity may be modulated by known neuroprotective agents such as estrogen (17β‐estradiol, E2). Human origin SH‐SY5Y neuroblastoma cells were differentiated into cholinergic phenotype by 10 μM retinoic acid over 6 days following, then E2 and hydrogen peroxide were treated respectively. E2 treatment reduced apoptotic changes including Bax:Bcl‐2 ratio and apoptosis‐related proteases caspase‐3, as well as neuronal cell death induced by oxidative stress. In addition, E2 treatment enhanced TERT expression and activity in neuronal cells. To characterize changes in NF‐κB and I‐κB expression/translocation, their protein levels were compared in cytosolic/nuclear fractions. The change in NF‐κB:I‐κB ratio was shown in neuronal cells following oxidative stress, then E2 attenuated NF‐κB transcriptional activity in neuronal cells. To determine whether TERT is required for the neuroprotective effects of estrogen in neuronal cells against oxidative stress, hTERT siRNA was employed. Specific knockdown of hTERT in E2‐treated cells showed significant apoptotic changes following oxidative stress, indicating cytoprotective effects of estrogen was lost in cells treated with hTERT knockdown. Taken together, these findings suggest that TERT is an essential mediator of estrogen neuroprotection.Support or Funding InformationNRF‐2014R1A1A3051724 to S.P., NRF‐2017R1A2A2A01067169 to Y.H., KGM4611714 to Y.H., Korea.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.