Stimulus-transcription coupling in catecholamine synthesis

儿茶酚胺合成中的刺激-转录耦合

• 批准号: 03670115
• 负责人: YANAGIHARA Nobuyuki
• 金额: $ 0.38万
• 依托单位: University of Occupational & Environmental Health, Japan
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670115/
• 关键词: Catecholamine synthesis; Cell stimulation; Ion channels; mRNA; Protein kinases; Second messengers; Transcriptional regulation; Tyrosine hydroxylase; カテコ-ルアミン; 生合成; 蛋白燐酸化反応; Ca^<2+>; calmodulinーdependent protein kinaseII

Long-term stimulation or persistent stress produces an in-crease in activity of tyrosine hydroxylase, the rate-limiting enzyme of catecholamine biosynthesis, in the sympathetic neurons and the adrenal medulla. The precise mechanism, however, still remains to be determined how cell stimulation increases the enzyme activity or protein (enzyme induction).In the present study, we used cultured bovine adrenal medullary cells as a model for catecholaminergic neuron and investigated as follows ; (A) cell stimulation-signal stransduction system, (B) cell stimulation-catecholamine synthesis coupling and (C) transcriptional regulation of tyrosine hydroxylase mRNA. Concerning about (A), we reported that (1) long treatment with okadaic acid reduced carbachol-evoked secretion of catecholamines by inhibiting Ca^<2+> influx in cultured adrenal medullary cells, (2) veratridine caused the Ca^<2+> -dependent increase in diacylglycerol formation and translocation of protein kinase C to memtbranes in adre … More nal medullary cells and (3) staurosporine effectively inhibited Ca^<2+> /calmodulin-dependent protein kinase II. Concerning about (B), we reported that (4) Brain natriuretic peptide stimulated the production of cyclin GMP and the activity of tyrosine hydroxylase in the cells, (5) sea urchin toxin inhibited nicotinic acetylcholine receptor-mediated synthesis and secretion of catecholamines and (6) lithium treatment stimulated catecholamine synthesis and secretion via activation of protein kinase C in cultured adrenal medullary cells. Concerning about (C), we observed that (7) okadaic acid stimulated the activity of tyrosine hydroxylase but attenuated the level of its mRNA and (8) hypertonic NaCl medium enhanced both the activity and mRNA of tyrosine hydroxylase in cultured adrenal medullary cells. It is interesting to note that there is a relationship between the activity and the mRNA level of tyrosine hydroxylase but not always. We must further study the coupling for cell stimulation-transcription of tyrosine hydroxylase in adrenal medulla as well as sympathetic neurons and the brain. Less

长期刺激或持续应激可引起交感神经元和肾上腺髓质中儿茶酚胺生物合成限速酶酪氨酸羟基酶活性升高。然而，细胞刺激如何增加酶活性或蛋白质(酶诱导)的确切机制仍有待确定。在本研究中，我们以培养的牛肾上腺髓质细胞作为儿茶酚胺能神经元的模型，研究了以下几个方面：(A)细胞刺激-信号转导系统，(B)细胞刺激-儿茶酚胺合成偶联和(C)酪氨酸羟基酶mRNA的转录调控。关于(A)，我们报道了(1)冈田酸长期处理通过抑制培养的肾上腺髓质细胞内钙内流而减少氨基甲胆碱诱导的儿茶酚胺的分泌，(2)藜芦碱引起肾上腺髓质细胞钙依赖的二酰甘油形成增加和蛋白激酶C移位到膜上。(2)在肾上腺髓质细胞(…)中，长期使用冈田酸可抑制钙离子内流，减少儿茶酚胺的分泌。关于(B)，我们报道了(4)脑利钠肽刺激细胞周期蛋白GMP的产生和酪氨酸羟基酶的活性，(5)海胆毒素抑制烟碱型乙酰胆碱受体介导的儿茶酚胺的合成和分泌，(6)锂处理通过激活蛋白激酶C促进肾上腺髓质细胞儿茶酚胺的合成和分泌。关于(C)，我们观察到(7)冈田酸刺激培养的肾上腺髓质细胞酪氨酸羟基酶的活性，但抑制其mRNA水平；(8)高渗盐可增强培养的肾上腺髓质细胞的酪氨酸羟基酶的活性和mRNA的表达。值得注意的是，酪氨酸羟化酶的活性与其mRNA水平之间存在一定的关系，但并不总是如此。我们必须进一步研究细胞刺激-肾上腺髓质以及交感神经元和脑中酪氨酸羟基酶转录的偶联。较少

项目成果

YANAGIHARA,N.: "Staurosporine:An effective infibitor for Ca_<2+>/ calmodulin-dependent protein kinase II." Journal of Neurochem.56. 294-298 (1991)

YANAGIHARA,N.：“星形孢菌素：Ca_2/钙调蛋白依赖性蛋白激酶 II 的有效抑制剂。”

Uezono,Y.: "Veratridine causes the Ca^<2+>-dependent increase in diacylglycerol formation and translocation of protein kinase C to membranes in cultured bovine adrenal medu llary cells" Naunyn-Schimiedeberg's Arch.Pharmacol.346. 76-81 (1992)

Uezono，Y.：“藜芦定导致Ca^2依赖性增加二酰基甘油的形成和蛋白激酶C易位到培养的牛肾上腺髓质细胞的膜上”Naunyn-Schimiedeberg的Arch.Pharmacol.346。

Sashihara,S.: "Overproduction of voltage-dependent Na^+ channels in the developing brain of genetically seizure-susceptible El mice." Neuroscience. 48. 285-291 (1992)

Sashihara,S.：“遗传性癫痫易感的 El 小鼠发育中大脑中电压依赖性 Na^2 通道的过度产生。”

NAKAGAWA,H.: "Inhibition of nicotinic acetylcholine receptor-mediated secretion and synthesis of catecholamines by urchin toxin in cultured bovine adrenal medullary cells." Biochem.Pharmacol.44. 1779-1785 (1992)

NAKAGAWA,H.：“在培养的牛肾上腺髓质细胞中，海胆毒素抑制烟碱乙酰胆碱受体介导的儿茶酚胺的分泌和合成。”

Yanagihara,N.: "Staurosporine : An effective inhibitor for Ca^<2+> /calmodulin-dependent protein kinase II" Journal of Neurochem. 56. 294-298 (1991)

Yanagihara，N.：“Staurosporine：Ca^2/钙调蛋白依赖性蛋白激酶II的有效抑制剂”《神经化学杂志》。