RESEARCH FOR TRANSMEMBRANE SIGNALING SYSTEM OF EPIDERMAL KERATINOCYTES ; INTRACELLULAR FREE CALCIUM AND PROTEIN KINASE C.

表皮角质细胞跨膜信号系统研究；

• 批准号: 05670717
• 负责人: KOIZUMI Hiroko
• 金额: $ 1.41万
• 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: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670717/
• 关键词: KERATINOCYTE; PROTEIN KINASE C; SPRR; PSORIASIS; CALCIUM; protein Kinase C; サブスタンスP; Keratinecyte; 魚鱗癬; adenylate cyclase; substance P; 培養ヒト表皮角化細胞; involucrin

Epidermal keratinocytes proiferate and differentiate to make stratum corneum. Many chemical mediators, hormones and peptides stimulate keratinocytes to induce phosphophatidylinositol metablism, 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 and diseased skin were observed. A new technique was reported to detect peroxide produced from keratinocytes using dihydrorhodamine 123. Differentiation associated expression of nPKC eta and SPRR was demonstrated in normal and diseased skin. The expression and cornified envelope formation are considered to mediated by activation of nPKC eta.Cross-talk among transmembrane signaling systems in keratinocytes, and drugs to influence these systems should be investigated. Abnormal keratinization and accerelation 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并分化形成角质层。许多化学介质、激素和肽刺激角质形成细胞，诱导磷脂酰肌醇代谢、细胞内游离钙的改变、腺苷酸环化酶反应激活。我们阐明缓激肽、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。显示了钙作为第二信使的重要性。通过免疫学检测膜骨架蛋白如血影蛋白、b-胞缝蛋白、4.1蛋白样蛋白的存在，并观察它们在培养的角质形成细胞和患病皮肤中分布的改变。据报道，一种新技术使用二氢罗丹明 123 检测角质形成细胞产生的过氧化物。在正常和患病皮肤中都证明了 nPKC eta 和 SPRR 的分化相关表达。表达和角质化包膜的形成被认为是由 nPKC eta 的激活介导的。角质形成细胞中跨膜信号系统之间的串扰以及影响这些系统的药物应该进行研究。角化异常和增殖加速被认为与银屑病的发病机制密切相关。牛皮癣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

Takano J,Koizumi H,Ohkawara A,Kamo N,Ueda T: "Ultraviolet action spectra for peroxide generation in human and pig epidermal keratinocytes loaded with dihydrorhodamine 123." Archives of Dermatological Research. 287. 321-325 (1995)

Takano J、Koizumi H、Ohkawara A、Kamo N、Ueda T：“负载二氢罗丹明 123 的人和猪表皮角质形成细胞中过氧化物生成的紫外线作用光谱。”

Koizumi H.: "Substance P induces inositol 1,4,5-trisphosphate and intracellular free calcium increase in cultured normal" human epidermal keratinocytes.Experimental Dermatology. 3(in press). (1994)

Koizumi H.：“P 物质诱导正常培养的人表皮角质形成细胞中肌醇 1,4,5-三磷酸和细胞内游离钙的增加。实验皮肤病学。

Koizumi H,Kumakiri M,Yamanaka K,Tomizawa K,Endo M,Ohkawara A: "Dermal denderocyte hamartoma, -A novel connective tissue hamartoma-" Journal of American Academy of Dermatology. 32 (2). 318-321 (1995)

Koizumi H、Kumakiri M、Yamanaka K、Tomizawa K、Endo M、Ohkawara A：“皮肤树突细胞错构瘤，-一种新型结缔组织错构瘤-”美国皮肤病学会杂志。

Takano J: "Ultraviolet action spectra for peroxide generation in human and pig epidermal keratinocytes loaded with dihydrorhodamine 123" Arch Dematol Res.287. 321-325 (1995)

Takano J：“载有二氢罗丹明 123 的人和猪表皮角质形成细胞中过氧化物生成的紫外线作用光谱”Arch Dematol Res.287。

小泉洋子: "ケラチノサイトの増殖調節 情報伝達系" 日本皮膚科学会雑誌. 103. 1614-1620 (1093)

小泉洋子：“调节角质细胞增殖的信息转导系统”日本皮肤病学会杂志 103. 1614-1620 (1093)。