Peroxisomal biogenesis in ischemic brain
Open accessAbstract
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.
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Peroxisome proliferation is induced through stimulation of PPARα activity in response to oxidative stress following ischemic injury in neurons.
“Peroxisome proliferation is induced through stimulation of peroxisome proliferator-activated receptor (PPAR) α activity in response to oxidative stress following ischemic injury in neurons (Young et al., 2015).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Young et al., 2015
Peroxisome proliferation can occur in response to cellular stress.
“Peroxisome proliferation can occur in response to cellular stress.”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Young et al., 2015
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The cell biology of the retinal pigment epithelium
Lakkaraju, A., Umapathy, A., Tan, L. X., Daniele, L., Philp, N. J., Boesze-Battaglia, K., & Williams, D. S. (2020) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2020.100846 · Cited by 422 · see citing works
- Authors
- Young, J. M., Nelson, J. W., Cheng, J., Zhang, W., Mader, S., Davis, C. M., Morrison, R. S., & Alkayed, N. J.
- Affiliations
- Oregon Health & Science University (US)
- University of Washington (US)
- Corresponding author
- Alkayed, Nabil J.
- ORCID
- Venue
- Antioxidants & Redox Signaling
- Publisher
- SAGE Publications
- Published
- 2015-01
- Volume
- 22
- Issue
- 2
- Pages
- 109-120
- ISSN
- 1523-0864 (ISSN-L)
- 1557-7716
- PMC
- PMC4281844
- OpenAlex
- W2335373300
- Cited by
- 21
- References
- 42
- Citations by year
- 2026: 4 · 2025: 2 · 2023: 2 · 2021: 3 · 2020: 4 · 2019: 1 · 2018: 2 · 2017: 1 · 2015: 2
- FWCI
- 0.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Antioxidants and Redox Signaling (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Washington
- Universität Heidelberg
- National Institutes of Health
- National Heart, Lung, and Blood Institute (T32HL094294)
- National Institute of Neurological Disorders and Stroke (R01NS044313, P30NS055088, P30NS061800, NS055088, R01NS070837, NS061800, R01NS035533)
- National Center for Research Resources (S10RR023432)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Keywords
- peroxisome biogenesis, cerebral ischemia, focal cerebral ischemia, catalase, peroxisomes, oxygen-glucose deprivation, neuronal cell death, Drp1, PPARα, neuroprotection, antioxidant defense, cortical neurons
- MeSH terms
- Animals, Catalase, Cell Survival, Glucose, Immunohistochemistry, Male, Mice, Inbred C57BL, Oxygen, Blotting, Western, Microscopy, Confocal, Dynamins, Mice
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