Ethanol impairs estrogen receptor signaling resulting in accelerated activation of senescence pathways, whereas estradiol attenuates the effects of ethanol in osteoblasts.
Ethanol impairs estrogen receptor signaling resulting in accelerated activation of senescence pathways, whereas estradiol attenuates the effects of ethanol in osteoblasts.
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DOI：
10.1359/jbmr.081011
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发表时间：
2009-02
期刊：
影响因子：
--
通讯作者：
Ronis MJ
中科院分区：
文献类型：
--
作者：
Chen JR;Lazarenko OP;Haley RL;Blackburn ML;Badger TM;Ronis MJ
流行病学和动物研究表明，长期饮酒是骨质疏松症的一个主要危险因素。在体外和体内长期灌注乙醇（EtOH）的雌性循环大鼠骨中，我们发现EtOH显著提高雌激素受体α (ERα)和β (ERβ) mRNA和ERα蛋白水平。体内和体外用17β-雌二醇（E2）处理可干扰EtOH对骨和成骨细胞的这些作用。ERα受体激动剂丙基吡唑三醇（PPT）和ERβ受体激动剂二乙基丙腈（DPN）分别减弱了乙醇诱导的ERα和ERβ基因的过表达。与ER拮抗剂ICI 182780类似，EtOH在UMR-106成骨细胞中阻断E2存在下ERα- ecfp的核易位。EtOH也下调ERE-luc报告基因的活性。另一方面，EtOH本身通过er -不依赖途径上调了一些常见的ERα和er β介导的基因。EtOH还可以反激活p21启动子区域的荧光素酶活性，而不需要额外的外源性ERα，激活p21和p53，并刺激大鼠基质成骨细胞中衰老相关的β-半乳糖苷酶活性。E2处理减弱了这些EtOH作用。我们得出结论，成骨细胞中EtOH和E2对er、p53/p21和细胞衰老的抑制串扰提供了一种病理生理机制，可能是暴露于酒精的女性骨质流失和雌激素保护作用的基础。
Epidemiological and animal studies have suggested that chronic alcohol consumption is a major risk factor for osteoporosis. Using bone from cycling female rats infused chronically with ethanol (EtOH) in vivo and osteoblastic cells in vitro, we found that EtOH significantly increased estrogen receptor α (ERα) and β (ERβ) mRNA and ERα protein levels. Treatment with 17β-estradiol (E2) in vivo and in vitro interfered with these effects of EtOH on bone and osteoblastic cells. ERα agonist propylpyrazoletriol (PPT) and ERβ agonist diarylpropionitrile (DPN) attenuated EtOH-induced ERα and ERβ gene overexpression, respectively. Similar to the ER antagonist ICI 182780, EtOH blocked nuclear translocation of ERα-ECFP in the presence of E2 in UMR-106 osteoblastic cells. EtOH also downregulated ERE-luc reporter activity. On the other hand, EtOH by itself upregulated some common ERα- and ERβ-mediated genes apparently by an ER-independent pathway. EtOH also transactivated the luciferase activity of the p21 promoter region independent of additional exogenous ERα, activated p21 and p53, and stimulated senescence-associated β-galactosidase activity in rat stromal osteoblasts. E2 treatment attenuated these EtOH actions. We conclude that inhibitory cross-talk between EtOH and E2 in osteoblasts on ERs, p53/p21, and cell senescence provides a pathophysiologic mechanism underlying bone loss and the protective effects of estrogens in alcohol-exposed females.
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DOI：
10.1083/jcb.151.6.1295
发表时间：
2000-12-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Porrello A;Cerone MA;Coen S;Gurtner A;Fontemaggi G;Cimino L;Piaggio G;Sacchi A;Soddu S
通讯作者：
Soddu S
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
64.5
作者：
Giorgio, M;Migliaccio, E;Pelicci, PG
通讯作者：
Pelicci, PG
影响因子：
3.8
作者：
Perrien, DS;Wahl, EC;Lumpkin, CK
通讯作者：
Lumpkin, CK
影响因子：
12.7
作者：
Chu, Jennifer;Tong, Ming;de la Monte, Suzanne M.
通讯作者：
de la Monte, Suzanne M.