Thyroid Hormones Protect Astrocytes from Morphine-Induced Apoptosis by Regulating Nitric Oxide and pERK 1/2 Pathways

Deb, Ishani and Das, Sumantra (2011) Thyroid Hormones Protect Astrocytes from Morphine-Induced Apoptosis by Regulating Nitric Oxide and pERK 1/2 Pathways. Neurochemistry International, 58 (8). pp. 861-871.

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    Abstract

    Unlike neurons and various other non-neuronal cells, astrocytes have been reported to be resistant to morphine induced cytotoxicity. The present work demonstrates that primary cultures of astrocytes are also sensitive to morphine toxicity depending upon the thyroidal status of the culture medium. Chronic morphine treatment of astrocytes, cultured under thyroid hormone (TH)-deficient conditions, induced apoptotic cell death which was characterized by nuclear condensation, DNA fragmentation and activation of caspase-3 like enzymes. Cell death was accompanied with increase in nNOS level, nitration of cellular proteins and down regulation of pAKT level. Phosphorylation of ERK1/2 showed a biphasic response, an initial induction followed by sustained decline during chronic morphine treatment and the initial induction of pERK1/2 level appeared to be critical for apoptosis in the cells. Interestingly, supplementation with normal levels of TH to cells attenuated morphine-induced apoptosis as well as the biphasic response of pERK1/2 in the astrocytes. However, in the presence of glutathione synthetase inhibitor L-buthionine-S,R-sulfoximine, TH failed to protect astrocytes. Overall, the study demonstrates a possible signaling mechanism of morphine induced toxicity to cells and suggests that alteration of glutathione homeostasis by TH protect astrocytes from morphine by regulating NO and pERK1/2 pathways in the cells.

    Item Type: Article
    URI: http://www.eprints.iicb.res.in/id/eprint/1316
    Subjects: Cell Biology & Physiology
    Divisions: Indian Institute of Chemical Biology
    Depositing User: Ms Sutapa Ganguly
    Date Deposited: 27 Jan 2012 12:01
    Last Modified: 27 Jan 2012 12:01
    Official URL: http://dx.doi.org/10.1016/j.neuint.2011.01.001
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