Influence of microcystins-LR (MC-LR) on autophagy in human neuroblastoma SK-N-SH cells

ABSTRACT

Microcystin-LR (MC-LR) variant exposure poses a potential health hazard to ecosystem, animals, and humans. Previously investigators showed that autophagy plays a key role in MC-LR induced cytotoxicity immortalized murine ovarian granular KK-1 cells and rat Sertoli cells. Recently exposure to MC-LR via drinking water was reported to accumulate in mouse brain with associated adverse oxidant and inflammatory responses. However, autophagy the physiological mechanism required for cells to degrade their own impaired organelles to maintain their homeostasis has not been determined with respect to MC-LR actions on the central nervous system (CNS). Thus, the aim of this study was to examine the effects of MC-LR on autophagy using human neuroblastoma SK-N-SH cells as CNS model. Data demonstrated that after treatment with 15 or 30 µmol/L MC-LR for 48 hr significantly reduced survival rate was noted in SK-N-SH cells. MC-LR increased the expression levels of autophagy-related proteins light chain 3 (LC3) II/I and p62 in SK-N-SH cells, resulting in the accumulation of LC3 and increased intracellular free calcium ion levels. Data indicated that MC-LR induced adverse effects on the CNS as evidenced by decreased cellular survival associated with inhibition of autophagy flux and consequent enhanced autophagosomes accumulation.

KEYWORDS:

• MC-LR
• autophagy flux
• nerve cell
• LC3

Acknowledgments

The authors are very grateful to Professor Sam Kacew from Canada for revising and polishing paper.

Additional information

Funding

This research was supported by the National Natural Science Foundation (81773393, 81502787), Central South University Innovation Driven Project (20170027010004), Key Research and Development Projects in Hunan Province (2019SK2041), National Science and Technology Basic Project of the Ministry of Science and Technology of China (2015FY111100, 2016YFC0900802).