Pathophysiological and pharmacological implications of mitochondria-targeted reactive oxygen species generation in astrocytes
- PMID: 18692534
- DOI: 10.1016/j.addr.2008.06.004
Pathophysiological and pharmacological implications of mitochondria-targeted reactive oxygen species generation in astrocytes
Abstract
Astrocytes, in addition to passively supporting neurons, have recently been shown to be actively involved in synaptic transmission and neurovascular coupling in the central nervous system (CNS). This review summarizes briefly our previous observations using fluorescent probes coupled with laser scanning digital imaging microscopy to visualize spatio-temporal alteration of mitochondrial reactive oxygen species (mROS) generation in intact astrocytes. mROS formation is enhanced by exogenous oxidants exposure, Ca2+ stress and endogenous pathological defect of mitochondrial respiratory complexes. In addition, mROS formation can be specifically stimulated by visible light or visible laser irradiation and can be augmented further by photodynamic coupling with photosensitizers, particularly with mitochondria-targeted photosensitizers. "Severe" oxidative insult often results in massive and homogeneous augmentation of mROS formation which causes cessation of mitochondrial movement, pathological fission and irreversible swelling of mitochondria and eventually apoptosis or necrosis of cells. Mitochondria-targeted antioxidants and protectors such as MitoQ, melatonin and nanoparticle C(60) effectively prevent "severe" mROS generation. Intriguingly, "minor" oxidative insults enhance heterogeneity of mROS and mitochondrial dynamics. "Minor" mROS formation-induced fission and fusion of mitochondria relocates mitochondrial network to form a mitochondria free gap, i.e., "firewall", which may play a crucial role in mROS-mediated protective "preconditioning" by preventing propagation of mROS during oxidative insults. These mROS-targeted strategies for either enhancement or prevention of mitochondrial oxidative stress in astrocytes may provide new insights for future development of therapeutic interventions in the treatment of cancer such as astrocytomas and gliomas and astrocyte-associated neurodegeneration, mitochondrial diseases and aging.
Similar articles
-
Critical role of mitochondrial reactive oxygen species formation in visible laser irradiation-induced apoptosis in rat brain astrocytes (RBA-1).J Biomed Sci. 2002;9(6 Pt 1):507-16. doi: 10.1159/000064723. J Biomed Sci. 2002. PMID: 12372988
-
Protective stabilization of mitochondrial permeability transition and mitochondrial oxidation during mitochondrial Ca2+ stress by melatonin's cascade metabolites C3-OHM and AFMK in RBA1 astrocytes.J Pineal Res. 2019 Jan;66(1):e12538. doi: 10.1111/jpi.12538. Epub 2018 Dec 2. J Pineal Res. 2019. PMID: 30415481
-
Visualization of melatonin's multiple mitochondrial levels of protection against mitochondrial Ca(2+)-mediated permeability transition and beyond in rat brain astrocytes.J Pineal Res. 2010 Jan;48(1):20-38. doi: 10.1111/j.1600-079X.2009.00721.x. Epub 2009 Nov 17. J Pineal Res. 2010. PMID: 19925580
-
Cationic antioxidants as a powerful tool against mitochondrial oxidative stress.Biochem Biophys Res Commun. 2013 Nov 15;441(2):275-9. doi: 10.1016/j.bbrc.2013.10.063. Epub 2013 Oct 22. Biochem Biophys Res Commun. 2013. PMID: 24161394 Review.
-
Pathological and Pharmacological Roles of Mitochondrial Reactive Oxygen Species in Malignant Neoplasms: Therapies Involving Chemical Compounds, Natural Products, and Photosensitizers.Molecules. 2020 Nov 11;25(22):5252. doi: 10.3390/molecules25225252. Molecules. 2020. PMID: 33187225 Free PMC article. Review.
Cited by
-
Mitochondria as the memory of preconditioning.Cond Med. 2021 Jun;4(3):151-160. Epub 2021 Aug 21. Cond Med. 2021. PMID: 36128004 Free PMC article.
-
Photochemical Targeting of Mitochondria to Overcome Chemoresistance in Ovarian Cancer †.Photochem Photobiol. 2023 Mar;99(2):448-468. doi: 10.1111/php.13723. Epub 2022 Oct 19. Photochem Photobiol. 2023. PMID: 36117466 Free PMC article. Review.
-
Crosstalk Between the Oxidative Stress and Glia Cells After Stroke: From Mechanism to Therapies.Front Immunol. 2022 Feb 25;13:852416. doi: 10.3389/fimmu.2022.852416. eCollection 2022. Front Immunol. 2022. PMID: 35281064 Free PMC article. Review.
-
VDACs: An Outlook on Biochemical Regulation and Function in Animal and Plant Systems.Front Physiol. 2021 Aug 5;12:683920. doi: 10.3389/fphys.2021.683920. eCollection 2021. Front Physiol. 2021. PMID: 34421635 Free PMC article. Review.
-
Priming Astrocytes With HIV-Induced Reactive Oxygen Species Enhances Their Trypanosoma cruzi Infection.Front Microbiol. 2020 Oct 19;11:563320. doi: 10.3389/fmicb.2020.563320. eCollection 2020. Front Microbiol. 2020. PMID: 33193149 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous