Oxidative stress-induced gene expression changes in prostate epithelial cells in vitro reveal a robust signature of normal prostatic senescence and aging.

Autor: Olascoaga S; Posgrado en Biología Experimental, DCBS, Universidad Autónoma Metropolitana Iztapalapa, Mexico City, Mexico.; Laboratorio de Bioenergética y Envejecimiento Celular, Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana (UAM), Mexico City, Mexico., Castañeda-Sánchez JI; División de Ciencias Biológicas y de la Salud, Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana-Xochimilco (UAM-X), Mexico City, Mexico., Königsberg M; Laboratorio de Bioenergética y Envejecimiento Celular, Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana (UAM), Mexico City, Mexico., Gutierrez H; Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, México. hgutierrez@inmegen.gob.mx., López-Diazguerrero NE; Laboratorio de Bioenergética y Envejecimiento Celular, Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana (UAM), Mexico City, Mexico. norm@xanum.uam.mx.
Jazyk: angličtina
Zdroj: Biogerontology [Biogerontology] 2024 Nov; Vol. 25 (6), pp. 1145-1169. Date of Electronic Publication: 2024 Aug 20.
DOI: 10.1007/s10522-024-10126-6
Abstrakt: Oxidative stress has long been postulated to play an essential role in aging mechanisms, and numerous forms of molecular damage associated with oxidative stress have been well documented. However, the extent to which changes in gene expression in direct response to oxidative stress are related to actual cellular aging, senescence, and age-related functional decline remains unclear. Here, we ask whether H 2 O 2 -induced oxidative stress and resulting gene expression alterations in prostate epithelial cells in vitro reveal gene regulatory changes typically observed in naturally aging prostate tissue and age-related prostate disease. While a broad range of significant changes observed in the expression of non-coding transcripts implicated in senescence-related responses, we also note an overrepresentation of gene-splicing events among differentially expressed protein-coding genes induced by H 2 O 2 . Additionally, the collective expression of these H 2 O 2 -induced DEGs is linked to age-related pathological dysfunction, with their protein products exhibiting a dense network of protein-protein interactions. In contrast, co-expression analysis of available gene expression data reveals a naturally occurring highly coordinated expression of H 2 O 2 -induced DEGs in normally aging prostate tissue. Furthermore, we find that oxidative stress-induced DEGs statistically overrepresent well-known senescence-related signatures. Our results show that oxidative stress-induced gene expression in prostate epithelial cells in vitro reveals gene regulatory changes typically observed in naturally aging prostate tissue and age-related prostate disease.
(© 2024. The Author(s).)
Databáze: MEDLINE
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