Cr(VI)-induced DNA damage is lessened by the modulation of hsp70 via increased GSH de novo synthesis in Drosophila melanogaster.
J Biochem Mol Toxicol
; 35(8): e22819, 2021 Aug.
Article
in En
| MEDLINE
| ID: mdl-34056787
ABSTRACT
Hexavalent chromium [Cr(VI)] is a genotoxic chemical, and in the chemical-exposed organism, oxidative stress is one of the leading causative mechanisms of genotoxicity. Heat shock protein-70 (Hsp70) is reported to be modulated in environmental chemical exposed organisms. Inadequate information on the protective role of Hsp70 in chemical-induced DNA lesions prompted us to investigate this possibility in a well-studied genetically tractable in vivo model Drosophila melanogaster. In the midgut cells of Cr(VI)-exposed hsp70-knockout (KO), -knockdown (KD), and -overexpression Drosophila strains, no significant change in double-strand breaks generation was observed in comparison to similarly exposed w 1118 and the respective genetic control strain after 48 h. Therefore, the role of hsp70 was investigated on oxidative DNA damage induction in the exposed organisms after 24 h. Oxidized DNA lesions (particularly oxidized purine-based lesions), 8-oxo-dG level, and oxidative stress endpoints were found to be significantly elevated in hsp70-KO and -KD strains in comparison to similarly exposed w 1118 and respective genetic control strain. On the contrary, in ubiquitous hsp70-overexpression strain exposed to Cr(VI), these endpoints were significantly lowered concurrently with increased GSH level through elevated gclc, and gclm expression, Gclc level, and GCL activity. The study suggests that as a consequence of hsp70 overexpression, the augmented GSH level in cells vis-a-vis GSH de novo synthesis can counteract Cr(VI)-induced oxidized DNA lesions.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA Damage
/
Chromium
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Oxidative Stress
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HSP70 Heat-Shock Proteins
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Drosophila Proteins
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Glutathione
Limits:
Animals
Language:
En
Journal:
J Biochem Mol Toxicol
Journal subject:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
TOXICOLOGIA
Year:
2021
Document type:
Article
Affiliation country:
India