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Arylamine N-acetyltransferase 1 protects against reactive oxygen species during glucose starvation: Role in the regulation of p53 stability
- Source :
- PLoS ONE, PLoS ONE, Vol 13, Iss 3, p e0193560 (2018)
- Publication Year :
- 2017
-
Abstract
- Human arylamine N-acetyltransferase 1 (NAT1) has been associated with cancer cell growth and invasion, but the underlying molecular mechanisms remain unknown. NAT1 is located on the short arm of chromosome 8 (8p21), a region that is commonly deleted in colon cancer. Previously, it was reported that HT-29 colon cancer cells, which have a large deletion at 8p21-22, show marked morphological changes, increased E-cadherin expression and altered cell-cell contact inhibition following down-regulation of NAT1 with shRNA. By contrast, no effects on growth were observed in HeLa cells. In the present study, cellular changes following knockout of NAT1 with CRISPR/Cas9 in HT-29 and HeLa cells were compared in the presence and absence of glucose. Cell growth decreased in both cell-lines during glucose starvation, but it was enhanced in HT-29 cells following NAT1 deletion. This was due to an increase in ROS production that induced cell apoptosis. Both ROS production and cell death were prevented by the glutathione precursor N-acetylcysteine. NAT1 knockout also resulted in a loss of the gain-of-function p53 protein in HT-29 cells. When p53 expression was inhibited with siRNA in parental HT-29 cells, ROS production and apoptosis increased to levels seen in the NAT1 knockout cells. The loss of p53 may explain the decreased colony formation and increased contact inhibition previously reported following NAT1 down-regulation in these cells. In conclusion, NAT1 is important in maintaining intracellular ROS, especially during glucose starvation, by stabilizing gain-of-function p53 in HT-29 cells. These results suggest that NAT1 may be a novel target to decrease intracellular gain-of -function p53.
- Subjects :
- 0301 basic medicine
Arylamine N-Acetyltransferase
Cultured tumor cells
lcsh:Medicine
Apoptosis
Biochemistry
Metastasis
HeLa
Gene Knockout Techniques
Oxidative Damage
Basic Cancer Research
Medicine and Health Sciences
Small interfering RNAs
RNA, Small Interfering
lcsh:Science
Multidisciplinary
biology
Cell Death
Chemistry
Organic Compounds
Monosaccharides
Cell biology
Isoenzymes
Nucleic acids
Oncology
Cell Processes
Physical Sciences
Cell lines
Biological cultures
HT29 Cells
Intracellular
Research Article
Programmed cell death
Blotting, Western
Carbohydrates
Cell Growth
03 medical and health sciences
DNA-binding proteins
Genetics
Humans
HeLa cells
Non-coding RNA
Cell Proliferation
Cell growth
lcsh:R
Organic Chemistry
Chemical Compounds
Contact inhibition
Biology and Life Sciences
Proteins
Cell Biology
biology.organism_classification
Cell cultures
Acetylcysteine
Gene regulation
Research and analysis methods
030104 developmental biology
Glucose
Cancer cell
RNA
lcsh:Q
Gene expression
CRISPR-Cas Systems
Tumor Suppressor Protein p53
Reactive Oxygen Species
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 13
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- PloS one
- Accession number :
- edsair.doi.dedup.....aa9dd1aeeab9e047e76d0720fdfc7630