Thyroid Hormones Protect Astrocytes from Morphine-Induced Apoptosis by Regulating Nitric Oxide and pERK 1/2 Pathways
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Thyroid Hormones Protect Astrocytes from Morphine-Induced Apoptosis by
Regulating Nitric Oxide and pERK 1/2 Pathways
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| Creator |
Deb, Ishani
Das, Sumantra |
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| Subject |
Cell Biology & Physiology
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| Description |
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.
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| Publisher |
Elsevier
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| Date |
2011
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/1316/1/NEUROCHEMISTRY_INTERNATIONAL___58_(_8_)_861%2D871;2011[70].pdf
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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| Relation |
http://dx.doi.org/10.1016/j.neuint.2011.01.001
http://www.eprints.iicb.res.in/1316/ |
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