Academic Journal
Humanin improved the rotenone-induced reactive oxygen species formation in PC12 cells by modulating the SIRT3/Nrf2/HO-1 signaling pathway.
| Title: | Humanin improved the rotenone-induced reactive oxygen species formation in PC12 cells by modulating the SIRT3/Nrf2/HO-1 signaling pathway. |
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| Authors: | Shan Y; The Institute of Toxicology, The Department of Preventive Medicine, The Third Military Medical University, Chongqing, China., Liu X; The Institute of Toxicology, The Department of Preventive Medicine, The Third Military Medical University, Chongqing, China., Ge W; The Institute of Toxicology, The Department of Preventive Medicine, The Third Military Medical University, Chongqing, China., Zhang Q; The Institute of Toxicology, The Department of Preventive Medicine, The Third Military Medical University, Chongqing, China., Yan S; The Institute of Toxicology, The Department of Preventive Medicine, The Third Military Medical University, Chongqing, China. |
| Source: | Toxicology and industrial health [Toxicol Ind Health] 2026 Aug; Vol. 42 (8), pp. 275-283. Date of Electronic Publication: 2026 Apr 27. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: SAGE Publications Country of Publication: England NLM ID: 8602702 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1477-0393 (Electronic) Linking ISSN: 07482337 NLM ISO Abbreviation: Toxicol Ind Health Subsets: MEDLINE |
| Imprint Name(s): | Publication: London : SAGE Publications Original Publication: Princeton, N.J. : Princeton Scientific Pub. Co. |
| MeSH Terms: | Rotenone*/toxicity , Reactive Oxygen Species*/metabolism , NF-E2-Related Factor 2*/metabolism , Sirtuin 3*/metabolism, Signal Transduction/drug effects ; Cell Survival/drug effects ; Oxidative Stress/drug effects ; Heme Oxygenase-1/metabolism ; Heme Oxygenase (Decyclizing)/metabolism ; Animals ; PC12 Cells ; Rats ; Sirtuins |
| Abstract: | ObjectiveMitochondrial dysfunction is the key factor in rotenone-induced neurotoxicity in dopaminergic neurons. This study aimed to investigate the role and potential mechanism of the mitochondrial DNA encoded peptide Humanin (HN) in alleviating rotenone-induced neurotoxicity.MethodsRotenone was added to the cultured PC12 cells to induce neurotoxicity. PC12 cells were preincubated with HN, which has a protective effect. Cell counting kit-8 (CCK-8) was used to evaluate PC12 cell viability. Flow cytometry to detect the content of reactive oxygen species (ROS) in PC12 cells. Western blot analysis was used to detect the expression of superoxide dismutase 2 (SOD2), acetylated SOD (Ac-SOD), sirtuin 3 (SIRT3), nuclear factor erythroid 2-related factor 2 (Nrf2), heme-oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase 1 (NQO1). The corresponding kits were used to measure the NAD+/NADH ratio and SOD content separately.ResultsHN pretreatment significantly increased PC12 cell survival, reduced ROS formation, and increased the NAD+/NADH ratio. It also increased the expression of SIRT3, Nrf2, HO-1, and NQO1 proteins and decreased the expression of Ac-SOD protein under rotenone exposure. At the same time, it also activated the Nrf2/HO-1 signaling pathway, which depends on HN-mediated SIRT3 activation.ConclusionThese results suggest that HN plays a protective role in rotenone-induced neurotoxicity by suppressing oxidative stress and activating the antioxidant response via the Nrf2/HO-1 pathway, which is regulated by SIRT3 in PC12 cells. |
| Competing Interests: | Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. |
| Contributed Indexing: | Keywords: Humanin; Nrf2/HO-1; SIRT3; mitochondrial-derived peptide; rotenone |
| Substance Nomenclature: | 03L9OT429T (Rotenone) 0 (Reactive Oxygen Species) 0 (NF-E2-Related Factor 2) 0 (Nfe2l2 protein, rat) EC 1.14.14.18 (Hmox1 protein, rat) EC 3.5.1.- (Sirtuin 3) 0 (SIRT3 protein, rat) EC 1.14.14.18 (Heme Oxygenase-1) EC 1.14.14.18 (Heme Oxygenase (Decyclizing)) EC 3.5.1.- (Sirtuins) |
| Entry Date(s): | Date Created: 20260427 Date Completed: 20260704 Latest Revision: 20260704 |
| Update Code: | 20260704 |
| DOI: | 10.1177/07482337261445494 |
| PMID: | 42041115 |
| Database: | MEDLINE |
| ISSN: | 1477-0393 |
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| DOI: | 10.1177/07482337261445494 |