Transmembrane signaling system concerning super oxide production

有关超氧化物产生的跨膜信号系统

• 批准号: 08670937
• 负责人: KOIZUMI Hiroko
• 金额: $ 1.47万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670937/
• 关键词: keratinocyte; superoxide; calcium; protein kinase C; H202; C-キナーゼ; cis-urocanic acid; ヒスタミン

UVB irradiation causes suppression of delayed hypersensitivity. Various photoreceptors and mediators of these changes have been proposed, one of which is cis-urocanic acid formed from the trans-urocanic acid in the epidermis naturally occurring on exposure to UV irradiation. The mechanism by which cis-urocanic acid alters the immune system is not fully clarified. Urocanic acid acts through different mechanisms, perhaps via histamine or histamine-like receptors. Histamine stimulation of keratinocytes induces activation of adenylate cyclase to accumulate cyclic AMP and an increase of intracellular Ca2+. Thus we investigated the effects of cis-urocanic acid on these transmembrane signaling systems in keratinocytes. Normal human keratinocytes were cultured in serum free KGM medium. Cyclic AMP was measured by radioimmunoassay. The alterations of intracellular Ca2+ in single living keratinocytes were measured using an inverted fluorescence microscope and an ARGUS-200/CA digital imaging system. Cis-urocanic acid itself did not induce adenylate cyclase activation in cultured normal human keratinocytes. Cis-urocanic acid inhibited cyclic AMP accumulation by histamine. Keratinocyte growth was not affected by cis-urocanic acid. Cis-urocanic acid did not induce an increase of intracellular Ca2+. Cis-urocanic acid attenuated the histamine induced increase in intracellular Ca2+ but not that induced by epinephrine. The effects of cis-urocanic acid on keratinocytes are revealed through modulation of effects of histamine.

UVB照射可抑制迟发性超敏反应。已经提出了这些变化的各种光感受器和介质，其中一种是由暴露于紫外线照射下表皮中自然产生的反式尿醛酸形成的顺式尿醛酸。顺式尿酸改变免疫系统的机制尚不完全清楚。尿尿酸通过不同的机制起作用，可能是通过组胺或组胺样受体。角质形成细胞的组胺刺激诱导腺苷酸环化酶的激活以积累环AMP和细胞内Ca2+的增加。因此，我们研究了顺式尿尿酸对角化细胞中这些跨膜信号系统的影响。正常人角质形成细胞在无血清KGM培养基中培养。用放射免疫法测定环AMP。使用倒置荧光显微镜和ARGUS-200/CA数字成像系统测量单个活角质形成细胞胞内Ca2+的变化。顺式尿酸本身在培养的正常人角质形成细胞中不诱导腺苷酸环化酶活化。顺式尿酸抑制组胺对环AMP的积累。顺式尿酸对角质细胞生长无影响。顺式尿酸不诱导细胞内Ca2+升高。顺式尿酸能减弱组胺诱导的细胞内Ca2+升高，但不能减弱肾上腺素诱导的细胞内Ca2+升高。顺式尿酸对角质形成细胞的影响是通过调节组胺的作用来揭示的。

项目成果

Shimizu T: "Immunoreactive analogues of erythrocyte ankyrin in human epidermal keratinocyte" Archives of Dermatological Research. 288. 19-23 (1996)

Shimizu T：“人表皮角质形成细胞中红细胞锚蛋白的免疫反应类似物”皮肤病学研究档案。

Shimizu T: "Cis-urocanic acid down-regulates histamine mediated activation of adenylate cyclase in pig epidermis" Acta Derm Venereol (Stockh). 78. 348-350 (1998)

Shimizu T：“顺式尿刊酸下调猪表皮中组胺介导的腺苷酸环化酶的激活”Acta Derm Venereol (Stockh)。

Koizumi H: "CD34 positive dendritic cells are intrinsic part of smooth muscle hamartoma." Br J Dermatol. in print.

Koizumi H：“CD34 阳性树突状细胞是平滑肌错构瘤的固有部分。”

Koizumi H.: "Differentiation associated licalization of small proline rich protein in normal and diseased skin" Br J Dermatol. 134. 686-692 (1996)

Koizumi H.：“正常和患病皮肤中富含脯氨酸的小蛋白的分化相关局部化”Br J Dermatol。

Koizumi H.: "Response to the letter by B.Yalcin et al (Normal serum adenosine deaminase activity in mycosis fungoides)" Acta Dermatol Venereol. 77. 404 (1997)

Koizumi H.：“对 B.Yalcin 等人的信件的回应（蕈样肉芽肿中正常血清腺苷脱氨酶活性）”Acta Dermatol Venereol。