Journal
TOXICOLOGY IN VITRO
Volume 87, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2022.105520
Keywords
Microcystin-LR; 3-MA; Autophagy; Apoptosis; Oxidative stress; Inflammation; GCO cell
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This study found that MC-LR can induce autophagy and apoptosis in GCO cells in vitro, and inhibition of autophagy can decrease the extent of apoptosis, induce more serious oxidative stress and inflammation, and eventually result in cell death. These findings provide some information for exploring the toxicity of MC-LR, but the role of autophagy in vivo requires further study.
MC-LR is one of the cyanotoxins produced by fresh water cyanobacteria. Previous studies showed that autophagy played an important role in MC-LR-induced reproduction toxicity. However, information on the toxicological mechanism is limited. In this study, MC-LR could induce autophagy and apoptosis in GCO cells in vitro. In GCO cells that had been exposed to MC-LR, the inhibitor of 3-MA effectively decreased cell viability and damaged cell ultrastructure. Oxidative stress was significantly increased in the 3-MA + MC-LR group, accompanied by significantly increased MDA content and decreased CAT activity and GST, SOD1, GPx, and GR expression levels (P < 0.05). Inflammation was more serious in the 3-MA + MC-LR group than that of MC-LR group, which was evidenced by increasing expression levels of TNF alpha, IL11, MyD88, TNFR1, TRAF2, JNK, CCL4, and CCL20 (P < 0.05). Interestingly, the significant decrease of Caspase-9, Caspase-7, and Bax expression and significant increase of Bcl-2 and Bcl-2/Bax ratio in 3-MA + MC-LR group compared to MC-LR group, suggesting that extent of apoptosis were reduced. Taken together, these results indicated that MC-LR induced autophagy and apoptosis in GCO cells, however, the inhibition of autophagy decreased the extent of apoptosis, induced more serious oxidative stress and inflammation, which eventually induced cell death. Our findings provided some information for exploring the toxicity of MC-LR, however, the role of autophagy require further study in vivo.
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