Amino acid deprivation induces TXNIP expression by NRF2 downregulation

Author:

Ahn Se Hee1,Jang Se-Kyeong1,Kim Yu Jin1,Kim Gyeongmi1,Park Ki Soo2,Jin Hyeon-Ok3,Park In-Chul3

Affiliation:

1. Korea Institute of Radiological & Medical Sciences

2. Konkuk University

3. Korea Institute of Radiological and Medical Sciences

Abstract

Abstract TXNIP is an essential regulator of cellular metabolism, including glucose homeostasis, fatty acid synthesis, cholesterol accumulation, and is implicated in metabolic diseases such as obesity, type 2 diabetes, and atherosclerosis. However, how TXNIP expression is regulated in response to amino acid (AA) deprivation is not well understood. In the present study, deprivation of AAs, especially arginine, glutamine, lysine, and methionine, induced TXNIP expression in H460 non-small cell lung cancer cells. Unexpectedly, TXNIP induction by AA deprivation was dependent on NRF2 downregulation, but not ATF4 activation. Furthermore, N-acetyl-L-cysteine, a scavenger of reactive oxygen species (ROS), prevented TXNIP expression in H460 cells deprived of AA. Taken together, TXNIP expression by AA deprivation is mediated by ROS production by NRF2 downregulation. Our findings suggest that TXNIP expression might be associated with the redox homeostasis of AA metabolism.

Publisher

Research Square Platform LLC

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