L-Cysteine mitigates ROS-induced apoptosis and neurocognitive deficits by protecting against endoplasmic reticulum stress and mitochondrial dysfunction in mouse neuronal cells.

Autor: Park SY; Laboratory of Immunobiology, School of Life Science, College of Natural Sciences, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 41566, Republic of Korea; AT-31 BIO Inc., Business Incubation Center, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 41566, Republic of Korea., Kim KY; Laboratory of Immunobiology, School of Life Science, College of Natural Sciences, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 41566, Republic of Korea; AT-31 BIO Inc., Business Incubation Center, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 41566, Republic of Korea., Gwak DS; Laboratory of Immunobiology, School of Life Science, College of Natural Sciences, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 41566, Republic of Korea., Shin SY; Department of Biological Sciences, Sanghuh College of Life Sciences, Konkuk University, Seoul 05029, Republic of Korea., Jun DY; AT-31 BIO Inc., Business Incubation Center, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 41566, Republic of Korea., Kim YH; Laboratory of Immunobiology, School of Life Science, College of Natural Sciences, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 41566, Republic of Korea; AT-31 BIO Inc., Business Incubation Center, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 41566, Republic of Korea. Electronic address: ykim@knu.ac.kr.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 Nov; Vol. 180, pp. 117538. Date of Electronic Publication: 2024 Oct 10.
DOI: 10.1016/j.biopha.2024.117538
Abstrakt: Oxidative stress and mitochondrial dysfunction play critical roles in neurodegenerative diseases. Glutathione (GSH), a key brain antioxidant, helps to neutralize reactive oxygen species (ROS) and maintain redox balance. We investigated the effectiveness of L-cysteine (L-Cys) in preventing apoptosis induced by the ROS generator 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) in mouse hippocampal neuronal HT22 cells, as well as alleviating memory and cognitive impairments caused by the GSH synthesis inhibitor L-buthionine sulfoximine (BSO) in mice. DMNQ-induced apoptotic events in HT22 cells, including elevated cytosolic and mitochondrial ROS levels, DNA fragmentation, endoplasmic reticulum stress, and mitochondrial damage-mediated apoptotic pathways were dose-dependently abrogated by L-Cys (0.5-2 mM). The reduced intracellular GSH level, caused by DMNQ treatment, was restored by L-Cys cotreatment. Although L-Cys did not significantly restore GSH in the presence of BSO, it prevented DMNQ-induced ROS elevation, mitochondrial damage, and apoptosis. Furthermore, compared to N-acetylcysteine and GSH, L-Cys had higher 2,2-diphenyl-1-picrylhydrazyl and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid radical-scavenging activity. L-Cys also restored mitochondrial respiration capacity in DMNQ-treated HT22 cells by reversing mitochondrial fission-fusion dynamic balance. BSO administration (500 mg/kg/day) in mice led to neuronal deficits, including memory and cognitive impairments, which were effectively mitigated by oral L-Cys (15 or 30 mg/kg/day). L-Cys also reduced BSO-induced ROS levels in the mice hippocampus and cortex. These findings suggest that even though it does not contribute to intracellular GSH synthesis, exogenous L-Cys protects neuronal cells against oxidative stress-induced mitochondrial damage and apoptosis, by acting as a ROS scavenger, which is beneficial in ameliorating neurocognitive deficits caused by oxidative stress.
Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest relevant to this study.
(Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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