Ammonium Increases Ca2+ Signalling and Up-Regulates Expression of TRPC1 Gene in Astrocytes in Primary Cultures and in the In Vivo Brain
Ammonium Increases Ca2+ Signalling and Up-Regulates Expression of TRPC1 Gene in Astrocytes in Primary Cultures and in the In Vivo Brain
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铵可增加原代培养物和体内脑星形胶质细胞中的 Ca2 信号传导并上调 TRPC1 基因的表达
DOI：
10.1007/s11064-014-1406-z
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发表时间：
2014-08
影响因子：
4.4
通讯作者：
Peng, Liang
中科院分区：
文献类型：
--
作者：
Du, Ting;Zhou, Jing;Verkhratsky, Alexei;Peng, Liang
脑内氨浓度的迅速升高是肝性脑病的主要致病因素，肝性脑病表现为精神错乱、健忘和易怒、精神病性症状、妄想、嗜睡、嗜睡，以及在终末阶段的昏迷。使用小鼠星形胶质细胞的原代培养物来研究用氯化铵慢性处理（3天）的效果（铵）3 mM，这是肝性脑病病症的相关浓度，对代谢型受体激动剂诱导的游离胞质Ca（2+）浓度[（Ca（2+））i]增加的影响，用基于Fura-2的显微荧光测定法和在用SERCA抑制剂毒胡萝卜素处理后激活的钙库操纵的Ca（2+）内流（SOCE）测量。使用的激动剂为β-肾上腺素能激动剂异丙肾上腺素、α2-肾上腺素能激动剂右美托咪定、InsP 3受体（InsP 3R）激动剂腺苷A和兰尼定受体激动剂4-氯间甲酚（4-CMC）。激动剂诱导的[Ca（2+）]i反应在长期暴露于铵的星形胶质细胞中显著增加。同样，由瞬时受体电位通道1（TRPC 1）介导的SOCE也显著增强。铵诱导的SOCE增加是星形胶质细胞中TRPC 1 mRNA和蛋白表达上调的结果。TRPC 1表达和SOCE的增加均被哇巴因拮抗剂坎利酮阻止。在腹腔注射尿素酶3天的成年小鼠脑中发现了类似的TRPC 1基因表达上调。在标记有星形胶质细胞特异性或神经元特异性标记物的转基因小鼠中，经腹膜内注射尿素酶处理3天，神经元和星形胶质细胞的荧光激活细胞分选表明TRPC 1 mRNA表达在星形胶质细胞中上调，但在神经元中不上调。
Rapid rise in ammonium concentration in the brain is the major pathogenic factor in hepatic encephalopathy that is manifested by state of confusion, forgetfulness and irritability, psychotic symptoms, delusions, lethargy, somnolence and, in the terminal stages, coma. Primary cultures of mouse astrocytes were used to investigate effects of chronic treatment (3 days) with ammonium chloride (ammonium) at 3 mM, this being a relevant concentration for hepatic encephalopathy condition, on metabotropic receptor agonist-induced increases in free cytosolic Ca(2+) concentration [(Ca(2+))i], measured with fura-2 based microfluorimetry and on store-operated Ca(2+) entry (SOCE) activated following treatment with the SERCA inhibitor thapsigargin. The agonists used were the β-adrenergic agonist isoproterenol, the α2-adrenergic agonist dexmedetomidine, the InsP3 receptor (InsP3R) agonist adenophostin A and ryanodine receptor agonist 4-Chloro-m-cresol (4-CMC). Agonist-induced [Ca(2+)]i responses were significantly increased in astrocytes chronically exposed to ammonium. Similarly, the SOCE, meditated by the transient receptor potential channel 1 (TRPC1), was significantly augmented. The ammonium-induced increase in SOCE was a result of an up-regulation of mRNA and protein expression of TRPC1 in astrocytes. Increase in TRPC1 expression and in SOCE were both prevented by ouabain antagonist canrenone. Similar up-regulation of TRPC1 gene expression was found in the brain of adult mice subjected to intraperitoneal injection of urease for 3 days. In transgenic mice tagged with an astrocyte-specific or a neurone-specific markers and treated with intraperitoneal injections of urease for 3 days, the fluorescence-activated cell sorting of neurones and astrocytes demonstrated that TRPC1 mRNA expression was up-regulated in astrocytes, but not in neurones.
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影响因子：
5.3
作者：
Montana V;Verkhratsky A;Parpura V
通讯作者：
Parpura V
DOI：
10.1016/j.bbamcr.2010.11.006
发表时间：
2011-05-01
影响因子：
5.1
作者：
Parpura, Vladimir;Grubisic, Vladimir;Verkhratsky, Alexei
通讯作者：
Verkhratsky, Alexei
影响因子：
4.4
作者：
L. Hertz;A. Schousboe;N. Boechler;S. Mukerji;S. Fedoroff
通讯作者：
L. Hertz;A. Schousboe;N. Boechler;S. Mukerji;S. Fedoroff
影响因子：
6.3
作者：
H. Sugimoto;R. Koehler;D. A. Wilson;S. Brusilow;R. Traystman
通讯作者：
H. Sugimoto;R. Koehler;D. A. Wilson;S. Brusilow;R. Traystman
DOI：
10.1007/bf02890308
发表时间：
1984
期刊：
Virchows Archiv B
影响因子：
--
作者：
J. O'connor;J. Renau‐Piqueras;S. Grisolía
通讯作者：
J. O'connor;J. Renau‐Piqueras;S. Grisolía