RESEARCH FOR TRANSMEMBRANE SIGNALING SYSTEM OF EPIDERMAL KERATINOCYTES; INTRACELLULAR FREE CALCIUM AND CELLULAR RESPONSES.

表皮角质细胞跨膜信号系统研究；

• 批准号: 02670469
• 负责人: KOIZUMI Hiroko
• 金额: $ 1.66万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02670469/
• 关键词: KERATINOCYTE; CALCIUM; PEROXIDE; SUBSTANCE P; PHOSPHOLIPASE C; PROTEIN KINASE C; ADENYLATE CYCLASE; PSORIASIS; Protein kinase C; phospholipase C; protein kinase C; adenylate cyclase; 細胞内遊離カルシウム; リポコルチン; フォドリン; エピネフリン

Epidermal keratinocytes proliferate and differentiate to make stratum corneum. Many chemical mediators, hormones and peptides stimulate keratinocytes to induce phosphophatidylinositol metabolism, alteration of intracellular free calcium, adenylate cyclase response activation. We elucidated that bradykinin, thrombin, substance P, beta-adrenarin, adenosine, and histamine induce increase of intracellular free calcium. These effects are mediated with synthesis of inositol 1,4,5-trisphosphate or adenylate cyclase activation. The importance of calcium as a second messenger is shown. Presence of membrane skeleton proteins such as spectrin, b-fodrin, 4.1 protein like proteins were detected immunologically and the alteration of their distribution in cultured keratinocytes were observed with the change of calcium concentration of the medium. A new technique was reported to detect peroxide produced from keratinocytes using dihydrorhodamine 123.Cross-talk among transmembrane signaling systems in keratinocytes, and drugs to influence these systems should be investigated. Abnormal keratinization and acceleration of proliferation are considered to closely realt to pathogenesis of psoriasis. The alteration of membrane signaling systems in psoriasis and the action mechanisms of the drugs used in therapy of skin diseases are under investigation.

表皮角质形成细胞增殖分化形成角质层。许多化学介质、激素和多肽刺激角质形成细胞诱导磷脂酰肌醇代谢，改变细胞内游离钙，激活腺苷酸环化酶反应。我们发现缓激肽、凝血酶、P物质、β -肾上腺素、腺苷和组胺可诱导细胞内游离钙的增加。这些作用是通过肌醇1,4,5-三磷酸合成或腺苷酸环化酶激活介导的。钙作为第二信使的重要性得到了证明。免疫检测到spectrin、b-fodrin、4.1蛋白样蛋白等膜骨架蛋白的存在，并观察其在培养的角质形成细胞中的分布随培养基钙浓度的变化而变化。报道了一种利用二氢霍达明123检测角质形成细胞产生的过氧化物的新技术。应该研究角化细胞跨膜信号系统之间的串扰，以及影响这些系统的药物。角化异常和增殖加速被认为与银屑病的发病密切相关。银屑病中膜信号系统的改变以及用于治疗皮肤病的药物的作用机制正在研究中。

项目成果

KOIZUMI H.: "Adenosine deaminase activity in serum of patients with psoriasis,mycosis fungoides,and adult T ccll leukemia." Acta Dermatovenereologica(Stockh). 72. 410-412 (1992)

KOIZUMI H.：“银屑病、蕈样肉芽肿和成人 Tccll 白血病患者血清中的腺苷脱氨酶活性。”

小泉 洋子: "角化異常とレチノイド." FRAGRANCE JOURNAL.20. 26-31 (1992)

小泉洋子：“角化不良和类维生素A。”《香水杂志》26-31 (1992)。

Shimizu T, Takakuwa Y, Koizumi H, Ishibashi T, Ohkawara A: "Immunoreactive analogues of erythrocyte ankyrin in human epidermal keratinocyte." Archives of Dermmatological Research.

Shimizu T、Takakuwa Y、Koizumi H、Ishibashi T、Ohkawara A：“人表皮角质形成细胞中红细胞锚蛋白的免疫反应类似物。”

小泉 洋子: "表皮細胞情報伝達系とカルシウム" 皮膚病診療. 14. (1992)

小泉洋子：“表皮细胞信号转导系统和钙”皮肤病理学 14。（1992）

小泉 洋子: "Protein kinase C." 皮膚科の臨床.

小泉洋子：“蛋白质激酶 C”。临床皮肤病学。