Microcystin‐LR‐Caused ROS generation involved in p38 activation and tau hyperphosphorylation in neuroendocrine (PC12) cells

• DOI: 10.1002/tox.21914
• Publication Date: 2013-10-19T06:58:40Z
• Authors: Guanmin Meng; Jinghui Liu; Shuyan Lin; Zonglou Guo; Lihong Xu
• Keywords: Hyperphosphorylation; Neurotoxicity; Tau protein

ABSTRACT Microcystin‐LR (MC‐LR), a potent specific hepatotoxin produced by cyanobacteria, has recently been reported to show neurotoxicity. Our previous study demonstrated that MC‐LR caused the reorganization of cytoskeleton architectures and hyperphosphorylation cytoskeletal‐associated proteins tau HSP27 in neuroendocrine PC12 cell line direct PP2A inhibition indirect p38 mitogen‐activated protein kinase (MAPK) activation. It shown oxidative stress is extensively associated with toxicity, mainly resulting from an excessive production reactive oxygen species (ROS). However, mechanisms which ROS mediates cytotoxic action are unclear. In present study, we investigated whether might play critical role MC‐LR‐induced microtubule‐associated activation MAPKs line. The results showed had time‐ concentration‐dependent effects on generation, p38‐MAPK phosphorylation. time‐course studies indicated similar biphasic changes generation hyperphosphorylation, started increase within 1 h reached maximum level at 3 followed decrease after prolonged treatment. Furthermore, pretreatment antioxidants, N ‐acetylcysteine vitamin C, significantly decreased effectively attenuated as well hyperphosphorylation. Taken together, these findings suggest triggered key intracellular event contributes induction phosphorylation, blockade this ROS‐mediated redox‐sensitive signal cascades may attenuate toxic MC‐LR. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 366–374, 2015.