Division of Biology, Department of Molecular Biology, Faculty of Arts and Sciences, Marmara University, Istanbul, Turkey.
Department of Software Engineering, Faculty of Engineering and Architecture, Beykoz University, Istanbul, Turkey.
Mol Biol Rep. 2022 Feb;49(2):1151-1159. doi: 10.1007/s11033-021-06942-5. Epub 2022 Jan 11.
Despite commonly use for treatment of type II diabetes, possible effects of glipizide on nuclear transport and DNA damage in cells are unknown. Since clinical response of glipizide may change with aging, the aim of the study was to investigate the effect of glipizide by comparing mature and senescent adipocytes.
The effects of glipizide were investigated in 3T3-L1 adipocytes. Effective and lethal doses were determined by real-time monitoring iCELLigence system. Comet assay was performed to determine DNA damage and quantitative PCR was conducted to detect gene expression levels. RAN expressions were found to be up regulated in mature 180 µM glipizide treated adipocytes compared to control group (p < 0.05); whereas down regulated in senescent 180 µM glipizide treated adipocytes compared to their control adipocytes (p < 0.05). Olive Tail Moment values were significantly higher in mature 180 µM glipizide treated adipocytes (MTG) and senescent 180 µM glipizide treated adipocytes (STG) comparing their untreated controls (p < 0.001 and p < 0.001 respectively). Also class 5 comets that shows severe DNA damage were found to be higher in both MTG and STG groups than their controls (p < 0.001 and p < 0.001, respectively). OTM values were higher in STG than MTG (p < 0.001).
This is the first study that reports glipizide caused DNA damage increasing with senescence in adipocytes. As a response to glipizide treatment Ran gene expression increased in mature; and decreased in senescent adipocytes. Further studies are needed to reveal the effect of glipizide on DNA and nuclear interactions in molecular level.
尽管格列吡嗪常用于治疗 2 型糖尿病，但它对细胞中核转运和 DNA 损伤的可能影响尚不清楚。由于格列吡嗪的临床反应可能随年龄而变化，因此本研究旨在通过比较成熟和衰老的脂肪细胞来研究格列吡嗪的作用。
在 3T3-L1 脂肪细胞中研究了格列吡嗪的作用。通过实时监测 iCELLigence 系统确定有效和致死剂量。进行彗星试验以确定 DNA 损伤，并用定量 PCR 检测基因表达水平。发现成熟的 180μM 格列吡嗪处理的脂肪细胞中 RAN 表达上调，与对照组相比（p<0.05）；而衰老的 180μM 格列吡嗪处理的脂肪细胞中 RAN 表达下调，与对照组相比（p<0.05）。与未处理的对照组相比，成熟的 180μM 格列吡嗪处理的脂肪细胞（MTG）和衰老的 180μM 格列吡嗪处理的脂肪细胞（STG）的橄榄尾矩值（OTM）显著升高（p<0.001 和 p<0.001）。还发现，这两种细胞的 5 级彗星，即显示严重 DNA 损伤的彗星，均高于各自的对照组（p<0.001 和 p<0.001）。与 MTG 相比，STG 的 OTM 值更高（p<0.001）。
这是第一项报道格列吡嗪在脂肪细胞中引起与衰老相关的 DNA 损伤增加的研究。作为对格列吡嗪治疗的反应，成熟脂肪细胞中 Ran 基因表达增加，而衰老脂肪细胞中表达减少。需要进一步的研究来揭示格列吡嗪在分子水平上对 DNA 和核相互作用的影响。
