Exposure to dithiocarbamate fungicide maneb in vitro and in vivo: Neuronal apoptosis and underlying mechanisms. (January 2023)

• Record Type: Journal Article
• Authors: Liu, Chaoyang; Liu, Zehua; Fang, Yanyan; Liao, Zizhuo; Zhang, Zhibing; Yuan, Xin; Yu, Ting; Yang, Yunying; Xiong, Min; Zhang, Xingyu; Zhang, Guoxin; Meng, Lanxia; Zhang, Zhentao
• Is Part Of: Environment international. Volume 171(2023)
• Publication Date: 2023-01
• Subjects: Maneb -- Neurotoxicity -- Mitochondrial dysfunction -- Apoptosis -- Parkinson's disease; Environmental protection -- Periodicals; Environmental health -- Periodicals; Environmental monitoring -- Periodicals; Environmental Monitoring -- Periodicals; Environnement -- Protection -- Périodiques; Hygiène du milieu -- Périodiques; Environnement -- Surveillance -- Périodiques; Environmental health; Environmental monitoring; Environmental protection; Periodicals; 333.705
• DOI: 10.1016/j.envint.2022.107696
• Languages: English
• ISSNs: 0160-4120

Abstract

Graphical abstract: Highlights: Maneb induces mitochondrial dysfunction and oxidative stress in dopaminergic cells. Maneb activates the mitochondrial apoptosis pathway in vitro and in vivo . The PKA/CREB signaling pathway is involved in maneb-induced apoptosis. Abstract: Maneb, a widely-used dithiocarbamate fungicide, remains in the environment and exerts adverse health effects. Epidemiological evidence shows that maneb exposure is associated with a higher risk of Parkinson's disease (PD), one of the most common neurodegenerative diseases. However, the molecular mechanisms underlying maneb-induced neurotoxicity remain unclear. Here we investigated the toxic effects and the underlying mechanisms of maneb on the degeneration of dopaminergic cells and α-synuclein in A53T transgenic mice. In SH-SY5Y cells, exposure to maneb reduces cell viability, triggers neuronal apoptosis, induces mitochondrial dysfunction, and generates reactive oxidative species (ROS) in a dose-dependent manner. Furthermore, Western blot analysis found that the mitochondrial apoptosis pathway (Bcl-2, Bax, cytochrome c, activated caspase-3) and the PKA/CREB signaling pathway (PKA, PDE10A, CREB, p-CREB) were changed by maneb both in vitro and in vivo . In addition, the activation of the mitochondrial apoptosis pathway induced by maneb was attenuated by activating PKA. Therefore, these results suggest that the PKA/CREB signaling pathway is involved in maneb-induced apoptosis. This study provides novel insights into maneb-induced neurotoxicity and the underlying mechanisms, which may serve as a guide for further toxicological assessment and standard application of maneb.