The role of antioxidants in restoring MAPK 14 and a DNA damage marker level following autophagy suppression.

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Autophagy deficiency is associated with the disruption of many intracellular biological processes. Using bioinformatics tools and fibroblast immunostaining technology, I tried to investigate whether oxidative stress is involved in mediating the effect of autophagy suppression on certain cell biological processes and signalling pathways. Many pharmaceutical components have different modes of action to suppress autophagy. In this study, I performed analysis on autophagy suppression induced by neutralizing lysosomal pH (NH4Cl and bafilomycin A1). Bioinformatics analysis of GEO data, GSE60570 accession number, revealed that p38 signalling induction and DNA damage response are among the main disrupted signalling pathways in bafilomycin A1-treated RPE-1 cells. Likewise, fibroblast immunostaining showed that autophagy deficiency established by ammonium chloride (NH4Cl) has significantly increased P38 signalling, DNA damage marker (H2A.X), and oxidative stress marker (dityrosine). I therefore investigated the role of oxidative stress and whether antioxidants treatment could reverse autophagy suppression effects on p38 signalling and DNA damage response. Importantly, antioxidant treatment clearly restored P38 signalling and H2A.X levels in autophagy-suppressed fibroblast cells. Indicating that oxidative stress might be associated with the harmful effect of autophagy suppression.", "claims": [{"id": "claim-method", "statement": "GSEA [22] was then used to test for enrichment against DNA damage response (MSigDB: M5464), MAPK pathway P38 (MSigDB: M12012) and Chuang oxidative stress response (MSigDB: M10970).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33292101", "locator": "sections[12] \"Gene set enrichment analysis\" paragraph 2", "quote": "GSEA [22] was then used to test for enrichment against DNA damage response (MSigDB: M5464), MAPK pathway P38 (MSigDB: M12012) and Chuang oxidative stress response (MSigDB: M10970)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "This article has no additional data.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33292101", "locator": "sections[17] \"Data accessibility\" paragraph 2", "quote": "This article has no additional data."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:33292101"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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