Non-genomic mechanisms mediate androgen-induced PSD95 expression
Non-genomic mechanisms mediate androgen-induced PSD95 expression
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非基因组机制介导雄激素诱导的 PSD95 表达
DOI：
10.18632/aging.101913
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发表时间：
2019-04
期刊：
影响因子：
5.2
通讯作者：
Cui Huixian
中科院分区：
文献类型：
--
作者：
Zhang Yizhou;Li Sha;Chen Huan;Chen Meiqin;Mi Shixiong;Ma Jingle;Wang Chang;Sun Hongmei;Liu Xiaoyun;Cui Huixian
雄激素诱导的突触可塑性的非基因组作用已被广泛研究。然而，潜在的机制仍然存在争议。我们最近发现，睾丸酮-胎牛血清白蛋白（T-BSA），细胞膜不可渗透的复合物，导致突触后密度95（PSD 95）蛋白水平的快速增加，通过转录非依赖性机制在小鼠海马HT 22细胞。使用T-BSA结合的FITC，我们验证了膜雄激素结合位点的存在。在这里，我们表明，T-BSA诱导的PSD 95表达介导的G-蛋白偶联受体（GPCR）-锌转运体ZIP 9（SLC 39 A9），雄激素膜结合位点之一，而不是膜定位的雄激素受体。此外，我们发现T-BSA诱导ZIP 9和Gnα11之间的相互作用，导致Erk 1/2 MAPK和eIF 4 E的磷酸化，这在mRNA翻译过程中是至关重要的。当ZIP 9或Gnα11表达被敲低或Erk 1/2激活被抑制时，PSD 95和p-eIF 4 E表达降低。综上所述，这些发现表明，ZIP 9通过Gnα11/Erk 1/2/eIF 4 E途径介导雄激素对HT 22细胞中突触蛋白PSD 95合成的非基因组作用。这一新的机制为了解雄激素的神经保护机制提供了理论基础。
The non-genomic actions of androgen-induced synaptic plasticity have been extensively studied. However, the underlying mechanisms remain controversial. We recently found that testosterone-fetal bovine serum albumin (T-BSA), a cell membrane-impermeable complex, led to a rapid increase in the postsynaptic density 95 (PSD95) protein level through a transcription-independent mechanism in mouse hippocampal HT22 cells. Using T-BSA conjugated FITC, we verified the presence of membrane androgen-binding sites. Here, we show that T-BSA-induced PSD95 expression is mediated by G-protein-coupled receptor (GPCR)-zinc transporter ZIP9 (SLC39A9), one of the androgen membrane binding sites, rather than the membrane-localized androgen receptor. Furthermore, we found that T-BSA induced an interaction between ZIP9 and Gnα11 that lead to the phosphorylation of Erk1/2 MAPK and eIF4E, which are critical in the mRNA translation process. The PSD95 and p-eIF4E expression decreased when knockdown of ZIP9 or Gnα11 expression or inhibition of Erk1/2 activation. Taken together, these findings suggest that ZIP9 mediates the non-genomic action of androgen on synaptic protein PSD95 synthesis through the Gnα11/Erk1/2/eIF4E pathway in HT22 cells. This novel mechanism provides a theoretical basis to understand the neuroprotective mechanism of androgen.
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DOI：
10.1016/j.tiv.2017.01.019
发表时间：
2017-04
期刊：
Toxicology in vitro : an international journal published in association with BIBRA
影响因子：
--
作者：
E. Gorowska-Wojtowicz;A. Hejmej;A. Kamińska;L. Pardyak;M. Kotula-Balak;J. Dulińska-Litewka;P. Laidler-P.-L
通讯作者：
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影响因子：
64.5
作者：
Yoon BC;Jung H;Dwivedy A;O'Hare CM;Zivraj KH;Holt CE
通讯作者：
Holt CE
影响因子：
16.2
作者：
Berry KP;Nedivi E
通讯作者：
Nedivi E
DOI：
10.2174/1871527315666151110125704
发表时间：
2016
期刊：
CNS & neurological disorders drug targets
影响因子：
--
作者：
Wahjoepramono EJ;Asih PR;Aniwiyanti V;Taddei K;Dhaliwal SS;Fuller SJ;Foster J;Carruthers M;Verdile G;Sohrabi HR;Martins RN
通讯作者：
Martins RN
影响因子：
2.7
作者：
Stough S;Kopec AM;Carew TJ
通讯作者：
Carew TJ