N‐acetylcysteine alleviated paraquat‐induced mitochondrial fragmentation and autophagy in primary murine neural progenitor cells

Abstract

The developing brain is uniquely vulnerable to toxic chemical exposures. Studies indicate that neural stem cell (NSC) self‐renewal is susceptible to oxidative stress caused by xenobiotics. However, the impact of antioxidants on NSC self‐renewal and the potential mechanisms remain elusive. In this study, primary murine neural progenitor cells (mNPCs) from the subventricular zone were used as a research model. In addition, paraquat (PQ) was used to elicit oxidative stress and N‐acetylcysteine (NAC) was used as a powerful antioxidant. mNPCs were treated with 80 μm PQ for 24 hours with or without 4 hours of NAC pretreatment. Our results showed that PQ treatment increased intracellular reactive oxygen species production, decreased cell viability and DNA synthesis, and promoted cell apoptosis. Meanwhile, pretreatment with NAC alleviated PQ‐induced cytotoxicity in mNPCs. To elucidate the mechanisms further, we found that NAC pretreatment prevented PQ‐induced reactive oxygen species production, mitochondrial fragmentation and autophagy in mNPCs. NAC‐pretreated cells showed increased anti‐apoptotic protein Bcl‐2 and decreased pro‐apoptotic protein Bax expression. Similarly, NAC pretreatment increased p‐mTOR and decreased LC3B‐II protein expression. Moreover, NAC decreased mitophagy related mRNA Pink1 and Parkin expression. Taken together, our results suggested that the antioxidant NAC treatment significantly attenuated PQ‐induced mNPC self‐renewal disruption through decreasing autophagy and salvaging mitochondrial morphology. These findings revealed a potential mechanism for neurological treatment relating to antioxidant and suggested potentially relevant implications for PQ‐related neurodegenerative disorders. Thus, our study also provided insight into therapeutic strategies for the neurotoxic effects of oxidative stress‐associated toxicants.

Cadmium inhibits neural stem/progenitor cells proliferation via MitoROS‐dependent AKT/GSK‐3β/β‐catenin signaling pathway

“…Newborn C57BL/6 mice were obtained from the Department of Laboratory Animals of Fudan University, and all experimental procedures were approved by the institutional animal care committee and conducted in accordance with Fudan University ethical guidelines. After hypothermic sacrifice, the SVZ were isolated from newborn C57BL/6J mice as previously described (Xiong et al, 2019). The obtained tissue was incubated in 0.05% trypsin–EDTA (Invitrogen, Carlsbad, CA) at 37°C for 3 min, then centrifuged for 5 min at 1000 rpm.…”

Nutraceuticals as Modulators of Autophagy: Relevance in Parkinson’s Disease

“…Some of the available papers reporting the ability of NAC to modulate the autophagy process are summarized in Table 8 . To start with, NAC supplementation has been found to alleviate paraquat-induced oxidative stress in primary murine neural progenitor cells, resulting in the suppression of autophagy and partial inhibition of Pink1 and Parkin -mediated mitophagy [ 189 ]. Another study reported that NAC attenuated olanzapine-induced overexpression of the LC3-II protein in mHypoA-59 hypothalamic neurons [ 190 ].…”

Physical exercise and mitochondrial function: New therapeutic interventions for psychiatric and neurodegenerative disorders

“…As differentiation of stem cells involves extensive cellular remodeling, autophagy ensures the elimination of unnecessary cellular components to maintain an optimal cellular status. It was demonstrated that pretreatment of antioxidant N-acetylcysteine (NAC) attenuated oxidative stress-induced NSCs' self-renewal disruption by suppressing autophagy signaling mTOR and decreased LC3B-II protein expression ( 59 ). In contrast, enhancing autophagy in aged satellite cells prevented the senescence and restored regenerative properties ( 60 ).…”