title: Remifentanil protects human keratinocytes against hypoxia-reoxygenation injury through activation of autophagy.
abstract: The proliferation, differentiation, and migration of keratinocytes are essential in the early stages of wound healing. Hypoxia-Reoxygenation (H/R) injury to keratinocytes can occur in various stressful environments such as surgery, trauma, and various forms of ulcers. The effects of remifentanil on human keratinocytes under hypoxia-reoxygenation have not been fully studied. Therefore, we investigated the effects of remifentanil on the proliferation, apoptosis, and autophagic activation of human keratinocytes during hypoxic-reoxygenation. Human keratinocytes were cultured under 1% oxygen tension for 24 h. The cells were then treated with various concentrations of remifentanil (0.01, 0.1, 0.5, and 1 ng/mL) for 2 h. Thereafter, the cells were reoxygenated for 12 h at 37°C. We measured cell viability via MTT assay. Using quantitative real-time PCR and western blot analysis, we measured the expression levels of proteins associated with apoptosis and autophagy. Quantification of apoptotic cells was performed using flow cytometer analysis and autophagic vacuoles were observed under a fluorescence microscope. Remifentanil treatment brought about an increase in the proliferation of human keratinocytes damaged by hypoxia-reoxygenation and decreased the apoptotic cell death, enhancing autophagic activity. However, the autophagy pathway inhibitor 3-MA inhibited the protective effect of remifentanil in hypoxia-reoxygenation injury. In conclusion, the current study demonstrated that remifentanil treatment stimulated autophagy and reduced apoptotic cell death in a hypoxia-reoxygenation model of human keratinocytes. Our results provide additional insights into the relationship between apoptosis and autophagy.
authors.affiliation: Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, Yangsan, Korea.
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Kwon
authors.affiliation: Department of Oral Anatomy, School of Dentistry, Pusan National University, Yangsan, Korea.
authors.forename: Bong-Soo
authors.initials: BS
authors.lastname: Park
authors.affiliation: Department of Oral Anatomy, School of Dentistry, Pusan National University, Yangsan, Korea.
authors.forename: Yong-Ho
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Pusan National University, Yangsan, Korea.
authors.forename: Yong-Deok
authors.initials: YD
authors.lastname: Kim
authors.affiliation: Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Pusan National University, Yangsan, Korea.
authors.forename: Cheul-Hong
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Pusan National University, Yangsan, Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Yoon
authors.affiliation: Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, Yangsan, Korea.
authors.forename: Ji-Uk
authors.initials: JU
authors.lastname: Yoon
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects*; D008954:Models, Biological; D010100:Oxygen / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D000077208:Remifentanil
chemical_list: D010880:Piperidines; D020011:Protective Agents; D000077208:Remifentanil; D010100:Oxygen