Abstract
The ATP-Binding Cassette (ABC) superfamily is the largest transporter family known to translocate a wide variety of exogenous and endogenous substrates across cell membranes. In this chapter we review the potential role of three ABC proteins in the transport of unconjugated bilirubin (UCB). These transporters are MRP1, MRP3 and PGP (MDR1). MRP1 is expressed at high levels in most epithelia, usually at the basolateral membrane. Among a multiplicity of substrates, MRP1 mediates the ATP-dependent cellular export of UCB, and its role has been demonstrated in protecting cells from UCB toxicity. MRP3 is an organic anion transporter whose major substrates are GSH conjugates of organic compounds. Among the MRP family members, MRP3 shares the highest degree of amino acid homology with MRP1. Although the hepatic expression of MRP3 has been reported to be up-regulated by bilirubin and bilirubin glucuronides, it is unknown whether MRP3 is also involved in the transport of UCB. PGP is expressed in organs involved in the elimination of endo- and xenobiotics and UCB is one of these substrates. Since the Km of PGP for UCB is well above pathophysiological levels of Bf, it remains uncertain whether it has a role in protecting against UCB cytotoxicity.
Keywords: ATP-binding-cassette protein (ABC) protein, multidrug-resistance-associated protein 1 (MRP1), multidrugresistance-associated protein 3 (MRP3), P-glycoprotein (PGP), unconiugated bilirubin, bilirubin neurocytotoxicity
Current Pharmaceutical Design
Title: The Role of ABC Transporters in Protecting Cells from Bilirubin Toxicity
Volume: 15 Issue: 25
Author(s): C. Bellarosa, G. Bortolussi and C. Tiribelli
Affiliation:
Keywords: ATP-binding-cassette protein (ABC) protein, multidrug-resistance-associated protein 1 (MRP1), multidrugresistance-associated protein 3 (MRP3), P-glycoprotein (PGP), unconiugated bilirubin, bilirubin neurocytotoxicity
Abstract: The ATP-Binding Cassette (ABC) superfamily is the largest transporter family known to translocate a wide variety of exogenous and endogenous substrates across cell membranes. In this chapter we review the potential role of three ABC proteins in the transport of unconjugated bilirubin (UCB). These transporters are MRP1, MRP3 and PGP (MDR1). MRP1 is expressed at high levels in most epithelia, usually at the basolateral membrane. Among a multiplicity of substrates, MRP1 mediates the ATP-dependent cellular export of UCB, and its role has been demonstrated in protecting cells from UCB toxicity. MRP3 is an organic anion transporter whose major substrates are GSH conjugates of organic compounds. Among the MRP family members, MRP3 shares the highest degree of amino acid homology with MRP1. Although the hepatic expression of MRP3 has been reported to be up-regulated by bilirubin and bilirubin glucuronides, it is unknown whether MRP3 is also involved in the transport of UCB. PGP is expressed in organs involved in the elimination of endo- and xenobiotics and UCB is one of these substrates. Since the Km of PGP for UCB is well above pathophysiological levels of Bf, it remains uncertain whether it has a role in protecting against UCB cytotoxicity.
Export Options
About this article
Cite this article as:
Bellarosa C., Bortolussi G. and Tiribelli C., The Role of ABC Transporters in Protecting Cells from Bilirubin Toxicity, Current Pharmaceutical Design 2009; 15 (25) . https://dx.doi.org/10.2174/138161209789058246
DOI https://dx.doi.org/10.2174/138161209789058246 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Recent Advances in Heterocyclic Tubulin Inhibitors Targeting the Colchicine Binding Site
Anti-Cancer Agents in Medicinal Chemistry Luminescent Silica Nanoparticles for Cancer Diagnosis
Current Medicinal Chemistry Anti-Seizure Medications and Estradiol for Neuroprotection in Epilepsy: The 2013 Update
Recent Patents on CNS Drug Discovery (Discontinued) Epigenetic Modification in Neuropathic Pain
Current Pharmaceutical Design Cyclin-Dependent Kinase 4/6 (Cdk4/6) Inhibitors: Perspectives in Cancer Therapy and Imaging
Mini-Reviews in Medicinal Chemistry Insulin-Like Growth Factor 1 Receptor Targeted Therapeutics: Novel Compounds and Novel Treatment Strategies for Cancer Medicine
Recent Patents on Anti-Cancer Drug Discovery Apolipoprotein E-mediated Modulation of ADAM10 in Alzheimer's Disease
Current Alzheimer Research Mitochondrial Respiration in the Platelets of Patients with Alzheimer’s Disease
Current Alzheimer Research Electrochemical DNA Biosensors in Drug Analysis
Current Pharmaceutical Analysis Ouabain-Induced Signaling and Cell Survival in SK-N-SH Neuroblastoma Cells Differentiated by Retinoic Acid
CNS & Neurological Disorders - Drug Targets Vitamin D Analogs as Anti-Carcinogenic Agents
Anti-Cancer Agents in Medicinal Chemistry ADAM19/Adamalysin 19 Structure, Function, and Role as a Putative Target in Tumors and Inflammatory Diseases
Current Pharmaceutical Design Dehydroepiandrosterone (DHEA) and its Sulphate (DHEAS) in Alzheimer’s Disease
Current Alzheimer Research Pharmacoproteomics Applications for Drug Target Discovery in CNS Disorders
Current Pharmacogenomics and Personalized Medicine The Need for Calcium Channels in Cell Proliferation
Recent Patents on Anti-Cancer Drug Discovery Dendritic Cells in Colorectal Cancer and a Potential for their Use in Therapeutic Approaches
Current Pharmaceutical Design Tumor Bone Diseases: Molecular Mechanisms and Opportunities for Novel Treatments
Current Medicinal Chemistry - Anti-Cancer Agents Selective Inhibitors of Zinc-Dependent Histone Deacetylases. Therapeutic Targets Relevant to Cancer
Current Pharmaceutical Design SiO2 NPs: Promising Candidates for Drug and Gene Delivery
Drug Delivery Letters Molecular and Cellular Activities of Vitamin E Analogues
Mini-Reviews in Medicinal Chemistry