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.
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.
Authors: Leen Hulshagen; Olga Krysko; Astrid Bottelbergs; Steven Huyghe; Rüdiger Klein; Paul P Van Veldhoven; Peter P De Deyn; Rudi D'Hooge; Dieter Hartmann; Myriam Baes Journal: J Neurosci Date: 2008-04-09 Impact factor: 6.167
Authors: Marc Fransen; Iulia Revenco; Hongli Li; Cláudio F Costa; Celien Lismont; Paul P Van Veldhoven Journal: Adv Exp Med Biol Date: 2020 Impact factor: 2.622
Authors: Marc Johnsen; Torsten Kubacki; Assa Yeroslaviz; Martin Richard Späth; Jannis Mörsdorf; Heike Göbel; Katrin Bohl; Michael Ignarski; Caroline Meharg; Bianca Habermann; Janine Altmüller; Andreas Beyer; Thomas Benzing; Bernhard Schermer; Volker Burst; Roman-Ulrich Müller Journal: J Am Soc Nephrol Date: 2020-02-28 Impact factor: 10.121
Authors: Aparna Lakkaraju; Ankita Umapathy; Li Xuan Tan; Lauren Daniele; Nancy J Philp; Kathleen Boesze-Battaglia; David S Williams Journal: Prog Retin Eye Res Date: 2020-02-24 Impact factor: 19.704
Authors: Fred D Mast; Thurston Herricks; Kathleen M Strehler; Leslie R Miller; Ramsey A Saleem; Richard A Rachubinski; John D Aitchison Journal: J Cell Biol Date: 2018-03-27 Impact factor: 10.539