Trans-resveratrol imparts disparate effects on transcription of DNA damage sensing/repair pathway genes in euglycemic and hyperglycemic rat testis
| Autor: | Maie D. Al-Bader, Mariam Alqaryyan, Narayana Kilarkaje |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Blood Glucose
Male 0301 basic medicine Programmed cell death Cell cycle checkpoint DNA Repair Transcription Genetic DNA damage Apoptosis Cell Cycle Proteins Biology Toxicology medicine.disease_cause 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Testis medicine Animals Rats Wistar Gene Pharmacology Cell Cycle Checkpoints Cell cycle Cell biology Disease Models Animal 030104 developmental biology Diabetes Mellitus Type 2 Gene Expression Regulation chemistry Resveratrol 030220 oncology & carcinogenesis Apoptosis Regulatory Proteins Carcinogenesis Biomarkers DNA DNA Damage |
| Zdroj: | Toxicology and Applied Pharmacology. 418:115510 |
| ISSN: | 0041-008X |
| DOI: | 10.1016/j.taap.2021.115510 |
| Popis: | Prevention or repair of DNA damage is critical to inhibit carcinogenesis in living organisms. Using quantitative RT2 Profiler™ PCR array, we investigated if trans-resveratrol could modulate the transcription of DNA damage sensing/repair pathway genes in euglycemic and non-obese type 2 diabetic Goto-Kakizaki rat testis. Trans-resveratrol imparted disparate effects on gene expressions. In euglycemic rats, it downregulated 79% and upregulated 2% of genes. However, in diabetic rats, it upregulated only 2% and downregulated 4% of genes. As such, diabetes upregulated 16% and downregulated 4% of genes. Trans-resveratrol normalized the expression of 9 (60%) out of 15 upregulated genes in diabetic rats. In euglycemic rats, trans-resveratrol inhibited ATM/ATR, DNA damage repair, pro-cell cycle progression, and apoptosis signaling genes. However, it increased Cdkn1a and Sumo1, indicating cell cycle arrest, apoptosis, and cytostasis in conjunction with increased DNA double-strand breaks and apoptosis. Diabetes increased DNA damage and apoptosis but did not affect ATM/ATR and double-strand break repair genes, although it increased few single-strand repair genes. Diabetes increased Abl1 and Sirt1, which may be related to apoptosis, but their increase may well suggest the enhanced cell cycle progression and putative carcinogenicity. The transcription of Rad17 and Smc1a increased in diabetic rats indicating G2 phase arrest and increases in a few DNA single-strand breaks repair genes suggesting DNA damage repair. Trans-resveratrol inhibits the cell cycle and causes cell death in euglycemic rat testis but normalizes diabetes-induced genes related to DNA damage and cell cycle control, suggesting its usefulness in maintaining DNA integrity in diabetes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect