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Imidazoline drugs stabilize lysosomes and inhibit oxidative cytotoxicity in astrocytes.

Authors
Choi, SH; Choi, DH; Lee, JJ; Park, MS; Chun, BG
Citation
Free radical biology & medicine, 32(5):394-405, 2002
Journal Title
Free radical biology & medicine
ISSN
0891-58491873-4596
Abstract
Oxidative stress is a primary pathogenesis in the brain, which is particularly vulnerable to oxidative stress. Maintenance of astrocyte functions under oxidative stress is essential to prevent neuronal injuries and to recover neuronal functions in various pathologic conditions. Imidazoline drugs have affinities for imidazoline receptors, which are highly distributed in the brain, and have been shown to be neuroprotective. This study presented the protective effects of several imidazoline drugs against oxidative cytotoxicity, in primary cultures of astrocytes. Imidazoline drugs, such as idazoxan, guanabenz, guanfacine, BU224, and RS-45041-190, showed protective effects against naphthazarin-induced oxidative cytotoxicity, as evidenced by LDH release and Hoechst 33342/propidium iodide staining. The imidazoline drugs stabilized lysosomes and inhibited naphthazarin-induced lysosomal destabilization, as evidenced by acridine orange relocation. Guanabenz inhibited, the leakage of lysosomal cathepsin D to cytosol, the decreased mitochondrial potential, and the release of mitochondrial cytochrome c, which were induced by naphthazarin. The lysosomal destabilization by oxidative stress and other apoptotic signals and subsequent cathepsin D leakage to the cytosol can induce apoptotic changes of mitochondria and eventually cell death. Therefore, lysosomal stabilization by imidazoline drugs may be ascribed to their protective effects against oxidative cytotoxicity.
MeSH terms
Acridine Orange/diagnostic useAdrenergic alpha-Antagonists/therapeutic useAnimalsAnimals, NewbornAntineoplastic Agents/adverse effects/*pharmacologyApoptosis/*drug effectsAstrocytes/drug effects/*metabolismCathepsin D/metabolismCell Division/*drug effectsCell LineCerebral Cortex/metabolismCytochrome c Group/metabolismFish VenomsGuanabenz/therapeutic useGuanfacine/therapeutic useHIV Protease Inhibitors/pharmacologyIdazoxan/therapeutic useImidazoles/*therapeutic useIndoles/therapeutic useIsoindolesL-Lactate Dehydrogenase/metabolismLigandsLysosomes/drug effects/*enzymologyMembrane Potentials/drug effectsMitochondria/physiologyNaphthoquinones/adverse effects/*pharmacologyNeuroglia/metabolismOxidation-ReductionPepstatins/pharmacologyProtease Inhibitors/pharmacologyRatsRats, Sprague-DawleyReactive Oxygen Species/metabolismReceptors, Drug
PMID
11864779
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pediatrics & Adolescent Medicine
AJOU Authors
박, 문성
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