PDS STUDY ON HUMAN PGP MDR TRANSPORTER ABCB1

人类 PGP MDR 转运蛋白 ABCB1 的 PDS 研究

• 批准号: 8364053
• 负责人: ELKA R GEORGIEVA
• 金额: $ 3.06万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8364053
• 关键词: ABCB1 gene; ATP-Binding Cassette Transporters; Anthracyclines; Brain; Cell membrane; Cells; Chemicals; Colon; Cytotoxic agent; D Cells; Dactinomycin; Drug Interactions; Drug Kinetics; Excretory function; Exhibits; Exposure to; Funding; Glycoproteins; Grant; Heat-Shock Response; Human; Intestines; Kidney; Liver; Mediating; Metabolism; Multi-Drug Resistance; National Center for Research Resources; Normal tissue morphology; P-Glycoprotein; Paclitaxel; Pharmaceutical Preparations; Phenotype; Physiological; Play; Principal Investigator; Process; Research; Research Infrastructure; Resistance; Resources; Roentgen Rays; Role; Small Intestines; Source; Stress; Taxoids; Technology; Toxic effect; Ultraviolet Rays; United States National Institutes of Health; Vinca Alkaloids; Xenobiotics; absorption; cancer cell; cost; drug market; inhibitor/antagonist; irradiation; tumor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. P-glycoprotein (Pgp, ABCB1), which belongs to the ATP-binding cassette (ABC) transporter superfamily, is a mammalian plasma membrane phospho-glycoprotein encoded by the multidrug resistance 1 (MDR1) gene. Pgp plays a role in the resistance of tumors to cytotoxic drugs and is known to efflux structurally unrelated diverse amphipathic compounds from cells. Pgp is expressed both in multidrug-resistant cancer cells and also in a number of normal tissues, such as those of the liver, kidney, small intestine, colon, and brain, suggesting that the physiological role of Pgp is a protective mechanism against xenobiotics and endogenous metabolites. After exposure to a single cytotoxic drug such as one of the Vinca alkaloids, anthracyclines, taxoids, or actinomycin D, cells can over-express Pgp and exhibit the MDR phenotype. Pgp over-expression is induced not only by chemical compounds, but also by physical stress caused by X-rays and ultraviolet light irradiation, or heat shock. Approximately 50% of currently marketed drugs have been identified to be Pgp substrates and/or inhibitors. Pgp can influence the pharmacokinetics of drugs by contributing to the processes that govern absorption, distribution, metabolism, elimination, and/or toxicity (ADMET). Additionally, Pgp has been implicated in drug-drug interactions involving co-administered Pgp substrates and modulators. For instance, intestinal Pgp mediates substantial direct transepithelial excretion of drugs including paclitaxel. ABCB1 is not oligomeric, but is homologous to dimeric prokaryotic ABC transporters, such as MsbA, which has been successfully studied at ACERT by Ku-band DEER.

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