PMID- 38054509
OWN - NLM
STAT- MEDLINE
DCOM- 20240320
LR  - 20240320
IS  - 1521-6551 (Electronic)
IS  - 1521-6543 (Linking)
VI  - 76
IP  - 4
DP  - 2024 Apr
TI  - Amino acid deprivation induces TXNIP expression by NRF2 downregulation.
PG  - 212-222
LID - 10.1002/iub.2792 [doi]
AB  - Thioredoxin-interacting protein (TXNIP) is sensitive to oxidative stress and is 
      involved in the pathogenesis of various metabolic, cardiovascular, and 
      neurodegenerative disorders. Therefore, several studies have suggested that TXNIP 
      is a promising therapeutic target for several diseases, particularly cancer and 
      diabetes. However, the regulation of TXNIP expression under amino acid 
      (AA)-restricted conditions is not well understood. In the present study, we 
      demonstrated that TXNIP expression was promoted by the deprivation of AAs, 
      especially arginine, glutamine, lysine, and methionine, in non-small cell lung 
      cancer (NSCLC) cells. Interestingly, we determined that increased TXNIP 
      expression induced by AA deprivation was associated with nuclear factor erythroid 
      2-related factor 2 (NRF2) downregulation, but not with activating transcription 
      factor 4 (ATF4) activation. Furthermore, N-acetyl-l-cysteine (NAC), a scavenger 
      of reactive oxygen species (ROS), suppressed TXNIP expression in NSCLC cells 
      deprived of AA. Collectively, the induction of TXNIP expression by AA deprivation 
      was mediated by ROS production, potentially through NRF2 downregulation. Our 
      findings suggest that TXNIP expression may be associated with the redox 
      homeostasis of AA metabolism and provide a possible rationale for a therapeutic 
      strategy to treat cancer with AA restriction.
CI  - (c) 2023 International Union of Biochemistry and Molecular Biology.
FAU - Ahn, Se Hee
AU  - Ahn SH
AD  - Division of Fusion Radiology Research, Korea Institute of Radiological & Medical 
      Sciences, Seoul, Republic of Korea.
AD  - Department of Biological Engineering, Konkuk University, Seoul, Republic of 
      Korea.
FAU - Jang, Se-Kyeong
AU  - Jang SK
AD  - Division of Fusion Radiology Research, Korea Institute of Radiological & Medical 
      Sciences, Seoul, Republic of Korea.
FAU - Kim, Yu Jin
AU  - Kim YJ
AD  - Division of Fusion Radiology Research, Korea Institute of Radiological & Medical 
      Sciences, Seoul, Republic of Korea.
AD  - Department of Biological Engineering, Konkuk University, Seoul, Republic of 
      Korea.
FAU - Kim, Gyeongmi
AU  - Kim G
AD  - Division of Fusion Radiology Research, Korea Institute of Radiological & Medical 
      Sciences, Seoul, Republic of Korea.
FAU - Park, Ki Soo
AU  - Park KS
AD  - Department of Biological Engineering, Konkuk University, Seoul, Republic of 
      Korea.
FAU - Park, In-Chul
AU  - Park IC
AD  - Division of Fusion Radiology Research, Korea Institute of Radiological & Medical 
      Sciences, Seoul, Republic of Korea.
FAU - Jin, Hyeon-Ok
AU  - Jin HO
AUID- ORCID: 0000-0002-1144-5991
AD  - KIRAMS Radiation Biobank, Korea Institute of Radiological & Medical Sciences, 
      Seoul, Republic of Korea.
LA  - eng
GR  - 50531-2023/Korea Institute of Radiological and Medical Sciences (KIRAMS), funded 
      by the Ministry of Science and ICT (MSIT)/
GR  - 50544-2023/Korea Institute of Radiological and Medical Sciences (KIRAMS), funded 
      by the Ministry of Science and ICT (MSIT)/
GR  - NRF-2022R1F1A1063450/National Research Foundation of Korea (NRF), funded by the 
      MIST/
GR  - NRF-2023R1A2C1003833/National Research Foundation of Korea (NRF), funded by the 
      MIST/
PT  - Journal Article
DEP - 20231206
PL  - England
TA  - IUBMB Life
JT  - IUBMB life
JID - 100888706
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Amino Acids)
RN  - 0 (TXNIP protein, human)
RN  - 0 (Carrier Proteins)
SB  - IM
MH  - Humans
MH  - Reactive Oxygen Species/metabolism
MH  - NF-E2-Related Factor 2/genetics/metabolism
MH  - Amino Acids/metabolism
MH  - Down-Regulation
MH  - *Carcinoma, Non-Small-Cell Lung
MH  - *Lung Neoplasms
MH  - Carrier Proteins/genetics/metabolism
OTO - NOTNLM
OT  - amino acid deprivation
OT  - non-small cell lung cancer
OT  - nuclear factor erythroid 2-related factor 2
OT  - reactive oxygen species
OT  - thioredoxin-interacting protein
EDAT- 2023/12/06 12:42
MHDA- 2024/03/20 06:45
CRDT- 2023/12/06 08:13
PHST- 2023/08/07 00:00 [received]
PHST- 2023/11/06 00:00 [accepted]
PHST- 2024/03/20 06:45 [medline]
PHST- 2023/12/06 12:42 [pubmed]
PHST- 2023/12/06 08:13 [entrez]
AID - 10.1002/iub.2792 [doi]
PST - ppublish
SO  - IUBMB Life. 2024 Apr;76(4):212-222. doi: 10.1002/iub.2792. Epub 2023 Dec 6.