Transient receptor potential channel 1/4 reduces subarachnoid hemorrhage-induced early brain injury in rats via calcineurin-mediated NMDAR and NFAT dephosphorylation.
Transient receptor potential channel 1/4 reduces subarachnoid hemorrhage-induced early brain injury in rats via calcineurin-mediated NMDAR and NFAT dephosphorylation.
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瞬时受体电位通道 1/4 通过钙调磷酸酶介导的 NMDAR 和 NFAT 去磷酸化减少大鼠蛛网膜下腔出血引起的早期脑损伤
DOI：
10.1038/srep33577
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发表时间：
2016-09-19
影响因子：
4.6
通讯作者：
Chen G
中科院分区：
文献类型：
--
作者：
Wang Z;Wang Y;Tian X;Shen H;Dou Y;Li H;Chen G
瞬时受体电位通道1/4（TRPC 1/4）被认为与蛛网膜下腔出血（SAH）引起的脑血管痉挛有关。本研究采用大鼠SAH模型，探讨TRPC 1/4在SAH后早期脑损伤（EBI）中的作用。原代培养的海马神经元暴露于氧合血红蛋白以模拟体外SAH。SAH后TRPC 1/4蛋白表达增加，5d达高峰。SKF 96365抑制TRPC 1/4可加重SAH诱导的EBI，如皮质细胞死亡（TUNEL染色）和变性（FJB染色）。此外，TRPC 1/4过表达可增加钙调神经磷酸酶活性，而钙调神经磷酸酶活性的增加可促进N-甲基-D-天冬氨酸受体（NMDAR）的去磷酸化。钙调磷酸酶拮抗剂FK 506可减弱TRPC 1/4过表达诱导的神经保护作用和NMDAR的去磷酸化作用。相反，钙调神经磷酸酶激动剂绿原酸抑制SAH诱导的EBI，即使当TRPC 1/4的siRNA干预进行。此外，钙调神经磷酸酶还可以导致活化T细胞核因子（NFAT）的核转移，NFAT是促进TRPC 1/4表达的转录因子。TRPC 1/4可通过钙调神经磷酸酶抑制NMDAR的磷酸化而抑制SAH诱导的EBI。TRPC 1/4诱导的钙调神经磷酸酶激活也可促进NFAT的核转移，提示TRPC 1/4表达的正反馈调节。
Transient receptor potential channel 1/4 (TRPC1/4) are considered to be related to subarachnoid hemorrhage (SAH)-induced cerebral vasospasm. In this study, a SAH rat model was employed to study the roles of TRPC1/4 in the early brain injury (EBI) after SAH. Primary cultured hippocampal neurons were exposed to oxyhemoglobin to mimic SAHin vitro. The protein levels of TRPC1/4 increased and peaked at 5 days after SAH in rats. Inhibition of TRPC1/4 by SKF96365 aggravated SAH-induced EBI, such as cortical cell death (by TUNEL staining) and degenerating (by FJB staining). In addition, TRPC1/4 overexpression could increase calcineurin activity, while increased calcineurin activity could promote the dephosphorylation of N-methyl-D-aspartate receptor (NMDAR). Calcineurin antagonist FK506 could weaken the neuroprotection and the dephosphorylation of NMDAR induced by TRPC1/4 overexpression. Contrarily, calcineurin agonist chlorogenic acid inhibited SAH-induced EBI, even when siRNA intervention of TRPC1/4 was performed. Moreover, calcineurin also could lead to the nuclear transfer of nuclear factor of activated T cells (NFAT), which is a transcription factor promoting the expressions of TRPC1/4. TRPC1/4 could inhibit SAH-induced EBI by supressing the phosphorylation of NMDAR via calcineurin. TRPC1/4-induced calcineurin activation also could promote the nuclear transfer of NFAT, suggesting a positive feedback regulation of TRPC1/4 expressions.
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影响因子：
6.2
作者：
Serrano-Perez, Maria C.;Fernandez, Miriam;Tranque, Pedro
通讯作者：
Tranque, Pedro
影响因子：
2.9
作者：
Bollimuntha, Sunitha;Ebadi, Manuchair;Singh, Brij B.
通讯作者：
Singh, Brij B.
影响因子：
4.7
作者：
Li, Hongyu;Huang, Junbo;Wang, Yizheng
通讯作者：
Wang, Yizheng
DOI：
10.1016/j.molbrainres.2003.07.005
发表时间：
2003-10-21
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Kato, A;Fukazawa, Y;Sugiyama, H
通讯作者：
Sugiyama, H
影响因子：
6.9
作者：
Gueresir, Erdem;Schuss, Patrick;Vatter, Hartmut
通讯作者：
Vatter, Hartmut