Ahmed Juvale Iman Imtiyaz, Abdul Hamid Azzmer Azzar, Abd Halim Khairul Bariyyah, Che Has Ahmad Tarmizi
Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia Health Campus, Kubang Kerian, Kota Bharu, 16150, Kelantan, Malaysia.
Department of Biotechnology, Kulliyyah of Science, International Islamic University Malaysia, Jalan Sultan Ahmad Shah, Bandar Indera Mahkota, 25200, Kuantan, Pahang, Malaysia.
Heliyon. 2022 Jun 22;8(6):e09777. doi: 10.1016/j.heliyon.2022.e09777. eCollection 2022 Jun.
The multidrug resistance phenomenon presents a major threat to the pharmaceutical industry. This resistance is a common occurrence in several diseases and is mediated by multidrug transporters that actively pump substances out of the cell and away from their target regions. The most well-known multidrug transporter is the P-glycoprotein transporter. The binding sites within P-glycoprotein can accommodate a variety of compounds with diverse structures. Hence, numerous drugs are P-glycoprotein substrates, with new ones being identified every day. For many years, the mechanisms of action of P-glycoprotein have been shrouded in mystery, and scientists have only recently been able to elucidate certain structural and functional aspects of this protein. Although P-glycoprotein is highly implicated in multidrug resistant diseases, this transporter also performs various physiological roles in the human body and is expressed in several tissues, including the brain, kidneys, liver, gastrointestinal tract, testis, and placenta. The expression levels of P-glycoprotein are regulated by different enzymes, inflammatory mediators and transcription factors; alterations in which can result in the generation of a disease phenotype. This review details the discovery, the recently proposed structure and the regulatory functions of P-glycoprotein, as well as the crucial role it plays in health and disease.
多药耐药现象对制药行业构成了重大威胁。这种耐药性在多种疾病中普遍存在，由多药转运蛋白介导，这些转运蛋白能主动将物质泵出细胞，使其远离靶区域。最著名的多药转运蛋白是P - 糖蛋白转运体。P - 糖蛋白内的结合位点可以容纳各种结构各异的化合物。因此，众多药物都是P - 糖蛋白的底物，而且每天都有新的底物被发现。多年来，P - 糖蛋白的作用机制一直笼罩在神秘之中，科学家直到最近才能够阐明该蛋白的某些结构和功能方面。尽管P - 糖蛋白与多药耐药性疾病密切相关，但这种转运蛋白在人体中也发挥着各种生理作用，并且在包括大脑、肾脏、肝脏、胃肠道、睾丸和胎盘在内的多个组织中表达。P - 糖蛋白的表达水平受不同的酶、炎症介质和转录因子调节；这些因素的改变可能导致疾病表型的产生。本综述详细介绍了P - 糖蛋白的发现、最近提出的结构和调节功能，以及它在健康和疾病中所起的关键作用。
