Dual functionality of myeloperoxidase in rotenone-exposed brain-resident immune cells

Chi Young Chang, Mi Jeon Song, Sae Bom Jeon, Hee Jung Yoon, Dae Kee Lee, In Hoo Kim, Kyungho Suk, Dong Kug Choi, Eun Jung Park

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


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.

Original languageEnglish
Pages (from-to)964-979
Number of pages16
JournalAmerican Journal of Pathology
Issue number2
StatePublished - Aug 2011

Bibliographical note

Funding Information:
Supported by the Korea Health Industry Development Institute (grant A090570-1002-0000100 ).


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