| Autor: |
Vijaya Prakash Krishnan Muthaiah, Kathiravan Kaliyappan, Supriya D. Mahajan |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Frontiers in Cell and Developmental Biology, Vol 11 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2296-634X |
| DOI: |
10.3389/fcell.2023.1047308 |
| Popis: |
Introduction: Poly ADP-Ribose Polymerase-1 (PARP1), a DNA repair enzyme is implicated as a key molecule in the pathogenesis of several neurodegenerative disorders. Traumatic insults inducing oxidative stress results in its over-activation causing inflammation and cell death (Parthanatos). As PARP1 inhibition is known to reduce oxidative stress, we hypothesized that PARP1 inhibition by a known inhibitor 3-aminobenzamide (3AB) might recuperate the damage in an in vitro model of blast injury using HEI-OC1 cells (mouse auditory hair cells).Methods: Here, we evaluated the protective effect of 3AB on HEI-OC1 cells following single and repetitive blast overpressures (BOPs).Results: We found that inhibition of PARP1 b 3AB inhibits the PARP1 enzyme and its action of a post-translational modification i.e. formation of Poly ADP-Ribose Polymers which leads to massive ATP depletion. PARP inhibition (3AB treatment) reduced the oxidative stress (4HNE, a marker of lipid peroxidation, and 8OHdG, a marker of oxidative DNA damage) in cells exposed to single/repetitive BOPS through up-regulation of Nrf2, a transcriptional regulator of antioxidant defense and the GCLC, a rate limiting enzyme in the synthesis of glutathione.Discussion: Overall, we found that PARP inhibition by 3AB helps to maintain the viability of BOP-exposed auditory hair cells by recuperating the ATP pool from both mitochondrial and glycolytic sources. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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