G6PD overexpression protects from oxidative stress and age-related hearing loss.

Aging Cell
Jose M Bermúdez-MuñozIsabel Varela-Nieto

Abstract

Aging of the auditory system is associated with the incremental production of reactive oxygen species (ROS) and the accumulation of oxidative damage in macromolecules, which contributes to cellular malfunction, compromises cell viability, and, ultimately, leads to functional decline. Cellular detoxification relies in part on the production of NADPH, which is an important cofactor for major cellular antioxidant systems. NADPH is produced principally by the housekeeping enzyme glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the rate-limiting step in the pentose phosphate pathway. We show here that G6PD transgenic mice (G6PD-Tg), which show enhanced constitutive G6PD activity and NADPH production along life, have lower auditory thresholds than wild-type mice during aging, together with preserved inner hair cell (IHC) and outer hair cell (OHC), OHC innervation, and a conserved number of synapses per IHC. Gene expression of antioxidant enzymes was higher in 3-month-old G6PD-Tg mice than in wild-type counterparts, whereas the levels of pro-apoptotic proteins were lower. Consequently, nitration of proteins, mitochondrial damage, and TUNEL+ apoptotic cells were all lower in 9-month-old G6PD-Tg than in wild-type counterparts. ...Continue Reading

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Citations

Sep 21, 2021·Frontiers in Cellular Neuroscience·Isabel Varela-NietoJosé Marco-Contelles

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Methods Mentioned

BETA
transgenic
PCR
Protein Assay
Assay

Software Mentioned

SPSS
SDS
Ensembl
Fiji
BioSigRP
IMARIS
SigGenRP
SigCal
Image Quant TL
Primer Express

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