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CYCLOSPORINE A AND SIGNAL TRANSDUCTION

环孢菌素 A 和信号转导

基本信息

批准号：
3140220
负责人：
SUDHIR GUPTA
金额：
$ 17.73万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-07-01 至 1992-03-31
项目状态：
已结题

项目摘要

Pleiotropic drug resistance is characterized by alterations in cell membrane properties. It has been shown that certain chemotherapeutic agents exert antineoplastic effect at the level of membrane. Cyclosporine A (CsA) partitions into phospholipid vesicles and interferes with plasma membrane phospholipid metabolism. It has also been shown to decrease the motional freedom of membrane lipids and to depolarize plasma membrane potentials in murine lymphoctyes. The overall aim of this proposal is to understand the effects of CsA on signal transduction pathway using both neoplastic (sensitive and pleiotropic drug resistant) and normal T and EBV-induced B cell lines. The specific aims of the study are: (1) To compare plasma membrane potentials in sensitive T and B leukemia cell lines and their corresponding drug resistant sublines, and in T and B cells lines derived from normal lymphocytes. The membrane potentials will be studied with DiOC5 dye using FACS. (2) To examine the effect of CsA on the generation of inositol trisphosphate in resistant and sensitive leukemic cell lines and T and B cell lines derived from normal lymphocytes. (3) To study the in vitro direct effect of CsA on the activation and translocation of protein kinase C (PKC) in tumor and normal lymphocyte-derived T and B cells lines. Studies will also be done to examine regulatory role of CsA on PMA-induced activation and translocation will be measured by immunoprecipitation and indirect immunofluorescence, using an alloantibody against PKC. (4) To examine the effect of CsA on membrane phosphorylation of P- 180. The studied would help in the understanding of the mechanisms of CsA on the early steps of lymphocyte activation and the mechanisms by which CsA corrects the pleiotropic drug resistance in neoplastic cells.

多效性耐药的特征是细胞内膜性能事实表明，某些化疗药物在一定水平上发挥抗肿瘤作用膜。环孢素A（CsA）分配到磷脂中囊泡和干扰质膜磷脂新陈代谢. 它也被证明可以减少运动自由的膜脂和去角质质膜在小鼠淋巴细胞中的潜力。其总体目标是建议是了解CsA对信号的影响使用肿瘤（敏感和敏感）的转导途径多效性耐药）和正常T和EBV诱导的B细胞线本研究的具体目的是：（1）比较血浆敏感T和B白血病细胞系的膜电位，其相应的耐药亚系，以及在T和B细胞中来源于正常淋巴细胞的细胞系。细胞膜电位将使用FACS用DiOC 5染料进行研究。 (2)审查 CsA对三磷酸肌醇生成的影响耐药和敏感白血病细胞系以及T和B细胞系来源于正常的淋巴细胞。 (3)研究体外直接 CsA对蛋白质活化和转运的影响肿瘤及正常淋巴细胞T、B中蛋白激酶C 细胞系还将进行研究，以审查 CsA对PMA诱导的活化和易位的影响将是通过免疫沉淀和间接免疫荧光，使用同种抗体对PKC。 (4)到检测CsA对P- 180. 研究将有助于理解 CsA对淋巴细胞活化早期的作用机制以及CsA纠正多效性药物的机制肿瘤细胞的耐药性。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Recent developments in clinical immunology.

临床免疫学的最新进展。

DOI：
10.2500/108854190778880204
发表时间：
1990
期刊：
Allergy proceedings : the official journal of regional and state allergy societies
影响因子：
0
作者：
Gupta,S
通讯作者：
Gupta,S

Correction of altered plasma membrane potentials. A possible mechanism of cyclosporin A and verapamil reversal of pleiotropic drug resistance in neoplasia.

纠正改变的质膜电位。