{"doi":"10.3390/antiox13060716","title":"Electrical Pulse Stimulation Protects C2C12 Myotubes against Hydrogen Peroxide-Induced Cytotoxicity via Nrf2/Antioxidant Pathway","abstract":"Skeletal muscle contraction evokes numerous biochemical alterations that underpin exercise benefits. This present study aimed to elucidate the mechanism for electrical pulse stimulation (EPS)-induced antioxidant adaptation in C2C12 myotubes. We found that EPS significantly upregulated Nrf2 and a broad array of downstream antioxidant enzymes involved in multiple antioxidant systems. These effects were completely abolished by pretreatment with a ROS scavenger, N-acetylcysteine. MitoSOX-Red, CM-H2DCFDA, and EPR spectroscopy revealed a significantly higher ROS level in mitochondria and cytosol in EPS cells compared to non-stimulated cells. Seahorse and Oroboros revealed that EPS significantly increased the maximal mitochondrial oxygen consumption rate, along with an upregulated protein expression of mitochondrial complexes I/V, mitofusin-1, and mitochondrial fission factor. A post-stimulation time-course experiment demonstrated that upregulated NQO1 and GSTA2 last at least 24 h following the cessation of EPS, whereas elevated ROS declines immediately. These findings suggest an antioxidant preconditioning effect in the EPS cells. A cell viability study suggested that the EPS cells displayed 11- and 36-fold higher survival rates compared to the control cells in response to 2 and 4 mM H2O2 treatment, respectively. In summary, we found that EPS upregulated a large group of antioxidant enzymes in C2C12 myotubes via a contraction-mitochondrial-ROS-Nrf2 pathway. This antioxidant adaptation protects cells against oxidative stress-associated cytotoxicity.","journal":"Antioxidants","year":2024,"id":442641,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9516,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":698952,"name":"Anjali Bhat","orcid":"0000-0001-8456-3668","position":1,"is_corresponding":false},{"id":715670,"name":"Cody Anderson","orcid":"0000-0003-2341-4962","position":2,"is_corresponding":false},{"id":1256393,"name":"Michael F. Allen","orcid":"0000-0001-5200-8758","position":3,"is_corresponding":false},{"id":1256852,"name":"Will Bruening","orcid":null,"position":4,"is_corresponding":false},{"id":1256853,"name":"Joël Jacob","orcid":null,"position":5,"is_corresponding":false},{"id":1082253,"name":"Ved Vasishtha Pendyala","orcid":null,"position":6,"is_corresponding":false},{"id":88931,"name":"Li‐Rong Yu","orcid":"0000-0001-6084-991X","position":7,"is_corresponding":false},{"id":704398,"name":"Taylor Bruett","orcid":null,"position":8,"is_corresponding":false},{"id":284842,"name":"Matthew C. Zimmerman","orcid":"0000-0001-5658-9051","position":9,"is_corresponding":false},{"id":320560,"name":"Song‐Young Park","orcid":"0000-0001-8576-7531","position":10,"is_corresponding":false},{"id":284731,"name":"Irving H. Zucker","orcid":"0000-0003-3636-7720","position":11,"is_corresponding":false},{"id":284729,"name":"Lie Gao","orcid":"0000-0002-7880-7213","position":12,"is_corresponding":false},{"id":1122661,"name":"Sarah Pribil Pardun","orcid":"0009-0003-4528-4836","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-19T02:01:20.107161Z","pmid":"38929155","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}