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Cross‐talk between IGF ‐1 and estrogen receptors attenuates intracellular changes in ventral spinal cord 4.1 motoneuron cells because of interferon‐gamma exposure
Author(s) -
Park Sookyoung,
Nozaki Kenkichi,
Smith Joshua A.,
Krause James S.,
Banik Naren L.
Publication year - 2014
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12520
Subject(s) - neuroprotection , insulin like growth factor , estrogen receptor , receptor , apoptosis , endocrinology , biology , medicine , tunel assay , growth factor , cytokine , microbiology and biotechnology , chemistry , pharmacology , immunology , cancer , breast cancer , biochemistry
Abstract Insulin‐like growth factor‐1 ( IGF ‐1) is a neuroprotective growth factor that promotes neuronal survival by inhibition of apoptosis. To examine whether IGF ‐1 exerts cytoprotective effects against extracellular inflammatory stimulation, ventral spinal cord 4.1 ( VSC 4.1) motoneuron cells were treated with interferon‐gamma ( IFN ‐γ). Our data demonstrated apoptotic changes, increased calpain:calpastatin and Bax:Bcl‐2 ratios, and expression of apoptosis‐related proteases (caspase‐3 and ‐12) in motoneurons rendered by IFN ‐γ in a dose‐dependent manner. Post‐treatment with IGF ‐1 attenuated these changes. In addition, IGF ‐1 treatment of motoneurons exposed to IFN ‐γ decreased expression of inflammatory markers (cyclooxygenase‐2 and nuclear factor‐kappa B:inhibitor of kappa B ratio). Furthermore, IGF ‐1 attenuated the loss of expression of IGF ‐1 receptors ( IGF ‐1Rα and IGF ‐1Rβ) and estrogen receptors ( ER α and ER β) induced by IFN ‐γ. To determine whether the protective effects of IGF ‐1 are associated with ER s, ER s antagonist ICI and selective si RNA targeted against ER α and ER β were used in VSC 4.1 motoneurons. Distinctive morphological changes were observed following si RNA knockdown of ER α and ER β. In particular, apoptotic cell death assessed by TUNEL assay was enhanced in both ER α and ER β‐silenced VSC 4.1 motoneurons following IFN ‐γ and IGF ‐1 exposure. These results suggest that IGF ‐1 protects motoneurons from inflammatory insult by a mechanism involving pivotal interactions with ER α and ER β.Pro‐inflammatory Th1 cytokine, IFN‐γ induced cellular damage was investigated in VSC4.1 motoneurons. IFN‐γ resulted in apoptosis and inflammatory changes in motoneurons. Apoptosis was mediated via up‐regulation of calpain and subsequent cleavage of caspase‐3. IGF‐1 is suggested as potentially neuroprotective in motoneuron following cytokine exposure. Cellular protective effects of IGF‐1 are mediated by cross‐talk with ERα and ERβ in VSC4.1 motoneurons.