NADPH Oxidase Mediates Membrane Androgen Receptor-Induced Neurodegeneration

Endocrinology
Mavis A A TenkorangRebecca L Cunningham

Abstract

Oxidative stress (OS) is a common characteristic of several neurodegenerative disorders, including Parkinson disease (PD). PD is more prevalent in men than in women, indicating the possible involvement of androgens. Androgens can have either neuroprotective or neurodamaging effects, depending on the presence of OS. Specifically, in an OS environment, androgens via a membrane-associated androgen receptor (mAR) exacerbate OS-induced damage. To investigate the role of androgens on OS signaling and neurodegeneration, the effects of testosterone and androgen receptor activation on the major OS signaling cascades, the reduced form of NAD phosphate (NADPH) oxidase (NOX)1 and NOX2 and the Gαq/inositol trisphosphate receptor (InsP3R), were examined. To create an OS environment, an immortalized neuronal cell line was exposed to H2O2 prior to cell-permeable/cell-impermeable androgens. Different inhibitors were used to examine the role of G proteins, mAR, InsP3R, and NOX1/2 on OS generation and cell viability. Both testosterone and DHT/3-O-carboxymethyloxime (DHT)-BSA increased H2O2-induced OS and cell death, indicating the involvement of an mAR. Furthermore, classical AR antagonists did not block testosterone's negative effects in an OS e...Continue Reading

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Citations

Apr 1, 2020·Biology of Sex Differences·Phong DuongRebecca L Cunningham
Oct 27, 2020·Oxidative Medicine and Cellular Longevity·Sandro PercárioMaria Fani Dolabela
Jun 3, 2021·Proceedings of the National Academy of Sciences of the United States of America·Daiki KajiokaGen Yamada
Sep 2, 2021·Endocrinology·Nathalie SumienRebecca L Cunningham

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