Glucose starvation impairs NER and γ-H2AX after UVB irradiation. (February 2023)

• Record Type: Journal Article
• Authors: Komaki, Yukako; Ono, Saki; Okuya, Takuto; Ibuki, Yuko
• Is Part Of: Toxicology in vitro. Volume 86(2023)
• Publication Date: 2023-02
• Subjects: Glucose -- γ-H2AX -- UV -- Repair -- DSBs; acetyl-CoA acetyl-coenzyme A -- ATM ataxia telangiectasia mutated -- ATP adenosine triphosphate -- ATR ataxia telangiectasia and Rad3 related protein -- BSA bovine serum albumin -- BSFGE biased sinusoidal field gel electrophoresis -- CPDs cyclobutane pyrimidine dimers -- DDR DNA damage response -- DMEM Dulbecco's modified Eagle's medium -- 2-DG 2-deoxy-d-glucose -- DSBs double strand breaks -- FADH2 dihydroflavin adenine dinucleotide -- FBS fetal bovine serum -- γ-H2AX phosphorylation of histone H2AX -- NAD nicotinamide adenine dinucleotide -- NER nucleotide excision repair -- 6-4PPs pyrimidine (6–4) pyrimidone photoproducts -- ssDNA single stranded DNA; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2022.105503
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: Glucose is the major source for energy production. As tumor cells have higher glucose requirement, combination of glucose restriction and radio- and chemo-therapy has been explored. In this study, impairment of UVB-induced DNA damage repair response (DDR) by glucose starvation was revealed. Human keratinocytes and skin carcinoma cells were cultured in medium containing 0, 2.5, 5.5 and 25 mM glucose. Glucose restriction suppressed cell proliferation and histone acetylation. UVB exposure formed similar levels of pyrimidine dimers in all glucose conditions, whereas the repair tended to be delayed in low glucose medium. The repair molecules, TFIIH and XPG, were accumulated to DNA damaged sites regardless of glucose supply levels, but the release was delayed in glucose-starved cells. The remaining pyrimidine dimers would induce the collapse of replication forks during S phase, resulting in phosphorylation of histone H2AX (γ-H2AX), but the γ-H2AX in cells cultured in glucose-deleted medium was unexpectedly decreased. This might be due to the suppression of DNA replication by glucose deletion. This was further confirmed by the decrease in the formation of DNA double strand breaks in glucose-starved cells. These results suggested that condition of energy supply might affect UV-induced DDR. Highlights: Glucose restriction decreased histone acetylation and γ-H2AX. The repair rate of UV-induced pyrimidine dimers was slower as the glucose decreased. A cause of the repair delay might be an impairment of NER molecule dynamics. Formation of UV-induced DSBs and γ-H2AX was suppressed by glucose starvation.