Imidazoline drugs stabilize lysosomes and inhibit oxidative cytotoxicity in astrocytes

Sang Hyun Choi, Dong Hee Choi, Jeong Jin Lee, Moon Sung Park, Boe Gwun Chun

    Research output: Contribution to journalArticlepeer-review

    30 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)394-405
    Number of pages12
    JournalFree Radical Biology and Medicine
    Volume32
    Issue number5
    DOIs
    Publication statusPublished - 2002 Mar 1

    Keywords

    • Astrocytes
    • BU224
    • Cathepsin D
    • Cytochrome c
    • Free radicals
    • Guanabenz
    • Guanfacine
    • Idazoxan
    • Lysosomal stability
    • Mitochondrial potential
    • Naphthazarin
    • RS-45041-190

    ASJC Scopus subject areas

    • Biochemistry
    • Physiology (medical)

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