Suppression of prolactin signaling by pyrrolidine dithiocarbamate is alleviated by N-acetylcysteine in mammary epithelial cells.

doi:10.1016/j.ejphar.2014.05.061

中山醫學大學機構典藏 CSMUIR > 醫學院 > 免疫學研究所 > 期刊論文 > Item 310902500/11734

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/11734

Title:	Suppression of prolactin signaling by pyrrolidine dithiocarbamate is alleviated by N-acetylcysteine in mammary epithelial cells.
Authors:	Wang, JH JY, Du YY, Wu MC, Chen CH, Huang HJ, Shen CF, Lee TH4, Lin Lee, YJ
Contributors:	中山醫學大學
Keywords:	Insulin;Mammary epithelial cells;PDTC;Prolactin;Signal transduction
Date:	2004
Issue Date:	2015-07-28T09:03:17Z (UTC)
ISSN:	0014-2999
Abstract:	Prolactin is the key hormone to stimulate milk synthesis in mammary epithelial cells. It signals through the Jak2-Stat5 pathway to induce the expression of β-casein, a milk protein which is often used as a marker for mammary differentiation. Here we examined the effect of pyrrolidine dithiocarbamate (PDTC) on prolactin signaling. Our results show that PDTC downregulates prolactin receptor levels, and inhibits prolactin-induced Stat5 tyrosine phosphorylation and β-casein expression. This is not due to its inhibitory action on NF-κB since application of another NF-κB inhibitor, BAY 11-7082, and overexpression of I-κBα super-repressor do not lead to the same results. Instead, the pro-oxidant activity of PDTC is involved as inclusion of the antioxidant N-acetylcysteine restores prolactin signaling. PDTC triggers great extents of activation of ERK and JNK in mammary epithelial cells. These do not cause suppression of prolactin signaling but confer serine phosphorylation of insulin receptor substrate-1, thereby perturbing insulin signal propagation. As insulin facilitates optimal β-casein expression, blocking insulin signaling by PDTC might pose additional impediment to β-casein expression. Our results thus imply that lactation will be compromised when the cellular redox balance is dysregulated, such as during mastitis. Copyright © 2014 Elsevier B.V. All rights reserved.
URI:	https://ir.csmu.edu.tw:8080/ir/handle/310902500/11734 http://dx.doi.org/10.1016/j.ejphar.2014.05.061
Relation:	Eur J Pharmacol. 2014 Sep 5;738:301-9.
Appears in Collections:	[免疫學研究所] 期刊論文

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