PreprintArticleVersion 1This version is not peer-reviewed
ARE/Nrf2 Transcription System Involved in Carotenoid, Polyphenol, and Estradiol Protection from Rotenone‐Induced Mitochondrial Oxidative Stress in Dermal Fibroblasts
Version 1
: Received: 17 July 2024 / Approved: 17 July 2024 / Online: 18 July 2024 (14:49:49 CEST)
How to cite:
Darawsha, A.; Trachtenberg, A.; Sharoni, Y. ARE/Nrf2 Transcription System Involved in Carotenoid, Polyphenol, and Estradiol Protection from Rotenone‐Induced Mitochondrial Oxidative Stress in Dermal Fibroblasts. Preprints2024, 2024071434. https://doi.org/10.20944/preprints202407.1434.v1
Darawsha, A.; Trachtenberg, A.; Sharoni, Y. ARE/Nrf2 Transcription System Involved in Carotenoid, Polyphenol, and Estradiol Protection from Rotenone‐Induced Mitochondrial Oxidative Stress in Dermal Fibroblasts. Preprints 2024, 2024071434. https://doi.org/10.20944/preprints202407.1434.v1
Darawsha, A.; Trachtenberg, A.; Sharoni, Y. ARE/Nrf2 Transcription System Involved in Carotenoid, Polyphenol, and Estradiol Protection from Rotenone‐Induced Mitochondrial Oxidative Stress in Dermal Fibroblasts. Preprints2024, 2024071434. https://doi.org/10.20944/preprints202407.1434.v1
APA Style
Darawsha, A., Trachtenberg, A., & Sharoni, Y. (2024). ARE/Nrf2 Transcription System Involved in Carotenoid, Polyphenol, and Estradiol Protection from Rotenone‐Induced Mitochondrial Oxidative Stress in Dermal Fibroblasts. Preprints. https://doi.org/10.20944/preprints202407.1434.v1
Chicago/Turabian Style
Darawsha, A., Aviram Trachtenberg and Yoav Sharoni. 2024 "ARE/Nrf2 Transcription System Involved in Carotenoid, Polyphenol, and Estradiol Protection from Rotenone‐Induced Mitochondrial Oxidative Stress in Dermal Fibroblasts" Preprints. https://doi.org/10.20944/preprints202407.1434.v1
Abstract
Cell aging is associated with the increased production of mitochondrial reactive oxygen species (mtROS) due to mitochondrial dysfunction, and various phytonutrients and estrogens have been shown to improve skin health. Thus, the aim of the current study was to examine damage to dermal fibroblasts by chemically-induced mitochondrial dysfunction and to study the mechanism of the protective effects of carotenoids, polyphenols, and estradiol. Rotenone, a Complex I inhibitor, caused mitochondrial dysfunction in human dermal fibroblasts, substantially reducing respiration and ATP levels, followed by increased mitochondrial and cytosolic ROS, which resulted in apoptotic cell death, increased matrix metalloproteinase-1 (MMP1) secretion, and decreased collagen secretion. Pre-treatment with carotenoid-rich tomato extracts, rosemary extract, and estradiol reversed these effects. These protective effects can be partially explained by a cooperative activation of antioxidant response element (ARE/Nrf2) transcriptional activity by the protective compounds and rotenone, which led to upregulation of antioxidant proteins such as NQO1. To determine if ARE/Nrf2 activity is crucial for cell protection, we inhibited it using the Nrf2 inhibitors ML385 and ochratoxin A. This inhibition markedly reduced the protective effects of the test compounds by diminishing their effect to reduce cytosolic ROS. Our study results indicate that phytonutrients and estradiol protect skin cells from damage caused by mitochondria-generated ROS and, thus, may delay skin aging and improve skin health.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
