Peroxisomal biogenesis in ischemic brain

Jennifer M. Young, Jonathan W. Nelson, Jian Cheng, Wenri Zhang, Sarah Mader, Catherine M. Davis, Richard S. Morrison, Nabil J. Alkayed

Research output: Contribution to journalReview article

9 Scopus citations

Abstract

Aims: Peroxisomes are highly adaptable and dynamic organelles, adjusting their size, number, and enzyme composition to changing environmental and metabolic demands. We determined whether peroxisomes respond to ischemia, and whether peroxisomal biogenesis is an adaptive response to cerebral ischemia. Results: Focal cerebral ischemia induced peroxisomal biogenesis in peri-infarct neurons, which was associated with a corresponding increase in peroxisomal antioxidant enzyme catalase. Peroxisomal biogenesis was also observed in primary cultured cortical neurons subjected to ischemic insult induced by oxygen-glucose deprivation (OGD). A catalase inhibitor increased OGD-induced neuronal death. Moreover, preventing peroxisomal proliferation by knocking down dynamin-related protein 1 (Drp1) exacerbated neuronal death induced by OGD, whereas enhancing peroxisomal biogenesis pharmacologically using a peroxisome proliferator-activated receptor-alpha agonist protected against neuronal death induced by OGD. Innovation: This is the first documentation of ischemia-induced peroxisomal biogenesis in mammalian brain using a combined in vivo and in vitro approach, electron microscopy, high-resolution laser-scanning confocal microscopy, and super-resolution structured illumination microscopy. Conclusion: Our findings suggest that neurons respond to ischemic injury by increasing peroxisome biogenesis, which serves a protective function, likely mediated by enhanced antioxidant capacity of neurons. Antioxid. Redox Signal. 22, 109-120.

Original languageEnglish (US)
Pages (from-to)109-120
Number of pages12
JournalAntioxidants and Redox Signaling
Volume22
Issue number2
DOIs
StatePublished - Jan 10 2015

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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    Young, J. M., Nelson, J. W., Cheng, J., Zhang, W., Mader, S., Davis, C. M., Morrison, R. S., & Alkayed, N. J. (2015). Peroxisomal biogenesis in ischemic brain. Antioxidants and Redox Signaling, 22(2), 109-120. https://doi.org/10.1089/ars.2014.5833