title: Dual functionality of myeloperoxidase in rotenone-exposed brain-resident immune cells.
abstract: Rotenone exposure has emerged as an environmental risk factor for inflammation-associated neurodegenerative diseases. However, the underlying mechanisms responsible for the harmful effects of rotenone in the brain remain poorly understood. Herein, we report that myeloperoxidase (MPO) may have a potential regulatory role in rotenone-exposed brain-resident immune cells. We show that microglia, unlike neurons, do not undergo death; instead, they exhibit distinctive activated properties under rotenone-exposed conditions. Once activated by rotenone, microglia show increased production of reactive oxygen species, particularly HOCl. Notably, MPO, an HOCl-producing enzyme that is undetectable under normal conditions, is significantly increased after exposure to rotenone. MPO-exposed glial cells also display characteristics of activated cells, producing proinflammatory cytokines and increasing their phagocytic activity. Interestingly, our studies with MPO inhibitors and MPO-knockout mice reveal that MPO deficiency potentiates, rather than inhibits, the rotenone-induced activated state of glia and promotes glial cell death. Furthermore, rotenone-triggered neuronal injury was more apparent in co-cultures with glial cells from Mpo(-/-) mice than in those from wild-type mice. Collectively, our data provide evidence that MPO has dual functionality under rotenone-exposed conditions, playing a critical regulatory role in modulating pathological and protective events in the brain.
authors.affiliation: Branches of Immune and Cell Therapy, National Cancer Center, Goyang, South Korea.
authors.forename: Chi Young
authors.initials: CY
authors.lastname: Chang
authors.forename: Mi Jeon
authors.initials: MJ
authors.lastname: Song
authors.forename: Sae-Bom
authors.initials: SB
authors.lastname: Jeon
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Yoon
authors.forename: Dae Kee
authors.initials: DK
authors.lastname: Lee
authors.forename: In-Hoo
authors.initials: IH
authors.lastname: Kim
authors.forename: Kyungho
authors.initials: K
authors.lastname: Suk
authors.forename: Dong-Kug
authors.initials: DK
authors.lastname: Choi
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Park
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002470:Cell Survival; D005260:Female; D006801:Humans; D007107:Immune System; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism; D009195:Peroxidase / Q000235:genetics / Q000502:physiology*; D010587:Phagocytosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012402:Rotenone / Q000494:pharmacology*; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D014475:Uncoupling Agents; D012402:Rotenone; D009195:Peroxidase