Ethanol induces apoptotic death of β-endorphin neurons in the rat hypothalamus by a TGF-β1-dependent mechanism
Ethanol induces apoptotic death of β-endorphin neurons in the rat hypothalamus by a TGF-β1-dependent mechanism
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DOI：
10.1111/j.1530-0277.2008.00627.x
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发表时间：
2008-04-01
影响因子：
3.2
通讯作者：
Sarkar, Dipak K.
中科院分区：
文献类型：
--
作者：
Kuhn, Peter;Sarkar, Dipak K.
Background: We have previously shown that developing beta-endorphin neurons, in the arcuate nucleus of the hypothalamus become increasingly apoptotic when exposed to ethanol. As in the previous study we have observed an involvement in transforming growth factor beta 1 (TGF-beta 1) in mediation of the apoptotic process, the present study was conducted to determine the ethanol-induced changes in this apoptotic regulatory peptide signaling in the arcuate nucleus of the hypothalamus of neonatal rats.Methods: Pups were exposed to 11.34% ethanol in a milk-based diet or control diet on postnatal day (PND) 3 to PND7. Two hours after the last daily feeding, brains were collected and frozen in liquid nitrogen for analysis of various apoptosis regulatory proteins in the arcuate tissue by Western blots. Some animals were fixed in 4% paraformaldehyde and analyzed immunohistochemically.Results: Ethanol exposure increased apoptotic death of beta-endorphin neurons in the arcuate nucleus of the hypothalamus. The cell death was associated with an increase in the tissue levels of TGF-beta 1 in the mediobasal hypothalamus. This was correlated with a reduction in the arcuate level of retinoblastoma protein (Rb) phosphorylation. The reduced level of Rb phosphorylation was associated with an increased protein level of the cyclin dependent kinase inhibitor p27/kip but with a decreased protein level of cyclin dependent kinase 4 and cyclin D3. In addition, the apoptotic cell death was positively correlated with the level of Bclxs but negatively correlated with the level of the Bcl2.Conclusions: These results suggest that ethanol exposure increases TGF-beta 1 signaling involving Bcl2 and Rb repression that may lead to apoptotic death of cells including beta-endorphin neurons in the arcuate nucleus of the hypothalamus.
