Table of contents
Volume 7, Issue 5, pp. 34 - 45, May 2023
Cover: Cover: This month in
Cell Stress: Implication of K+ channels in mycotoxin toxicity. Image depicts structure of human potassium channel K2P1. PDB ID: 3UKM. Long, S.B., Miller, A.N. (2011) Crystal structure of the human two-pore domain potassium channel K2P1. Science 335: 432-436. Modified by
Cell Stress. The cover is published under the CC BY 4.0 license.
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CRISPR-activation screen identified potassium channels for protection against mycotoxins through cell cycle progression and mitochondrial function
Yulong Tang, Simeng Liao, Zhuyuan Nie, Guangwei Kuang, Chunxiao Ji, Dan Wan, Liuqin He, Fengna Li, Xiangfeng Kong, Kai Zhan, Bie Tan, Xin Wu and Yulong Yin
Research Articles |
page 34-45 | 10.15698/cst2023.05.279 | Full text | PDF |
Abstract
Zearalenone (ZEA) exposure has carcinogenic effects on human and animal health by exhibiting intestinal, hepatic, and renal toxicity. At present, the underlying mechanisms on how ZEA induces apoptosis and damage to tissues still remain unclear. In this study, we aimed to identify genes that modulate the cellular response to ZEA using clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 screening, and further validate novel gene functions to elucidate molecular mechanisms underlying particular biological processes in vivo and in vitro. Two ZEA-resistant cell lines, designated Ov-KCNJ4 and Ov-KCNJ12, were yielded by CRISPR activation screening which had significant changes in ZEA resistance and growth rates. Results showed that ZEA could interact with the cell membrane proteins KCNJ4 and KCNJ12, inducing cell cycle arrest, disruption of DNA replication and base excision repair. Overexpression of KCNJ4 and KCNJ12 was involved in ZEA resistance by regulating cell cycle to neutralize toxicity, sustaining mitochondrial morphology and function via attenuating the damage from oxidative stress in the KCNJ4-mitoKATP pathway. In vivo experiments showed that AAV-KCNJ4 delivery significantly improved ZEA-induced renal impairment and increased antioxidative enzyme activity by improving mitochondrial function. Our findings suggest that increasing potassium channel levels may be a putative therapeutic target for mycotoxin-induced damage.
