title: Expression of ATP-Binding Cassette Transporters B1 and C1 after Severe Traumatic Brain Injury in Humans.
abstract: Adenosine triphosphate-binding cassette (ABC) transport proteins ABCC1 and ABCB1 (also known as multidrug resistance-associated protein 1 and p-glycoprotein, respectively), are key membrane efflux transporters of drugs and endogenous substrates, including in the brain. The impact of traumatic brain injury (TBI) on ABCC1 and ABCB1 expression in humans is unknown. We hypothesized that ABCC1 and ABCB1 expression would be altered in brain tissue from patients acutely after severe TBI. Archived TBI samples (n=10) from our Brain Trauma Research Center and control samples (n=7) from our Alzheimer Disease Research Center were obtained under Institutional Review Board approval. Protein was extracted from fresh frozen cortical brain tissue for Western blot analysis and sections were obtained from fixed cortical tissue for immunohistochemistry. Relative abundance of ABCC1 was increased in samples from TBI versus controls (2.8±2.5 fold; p=0.005). ABCC1 immunohistochemistry was consistent with Western blot data, with increased immunoreactivity in cerebral blood vessel walls, as well as cells with the morphological appearance of neurons and glia in TBI versus controls. Relative abundance of ABCB1 was similar between TBI and controls (p=0.76), and ABCB1 immunoreactivity was primarily associated with cerebral blood vessels in both groups. These human data show that TBI increases ABCC1 expression in the brain, consistent with possible implications for both patients receiving pharmacological inhibitors and/or substrates of ABCC1 after TBI.
authors.affiliation: 1 Department of Critical Care Medicine, University of Pittsburgh School of Medicine , the Safar Center for Resuscitation Research and the Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.|7 Phoenix Children's Children's Hospital, Critical Care, and the University of Arizona , Phoenix, Arizona.
authors.forename: F Anthony
authors.initials: FA
authors.lastname: Willyerd
authors.affiliation: 2 Department of Pharmacy and Therapeutics, School of Pharmacy, University of Pittsburgh , Pittsburgh, Pennsylvania.|6 Clinical and Translational Science Institute, University of Pittsburgh School of Medicine , the Safar Center for Resuscitation Research and the Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.
authors.forename: Philip E
authors.initials: PE
authors.lastname: Empey
authors.affiliation: 2 Department of Pharmacy and Therapeutics, School of Pharmacy, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Ashley
authors.initials: A
authors.lastname: Philbrick
authors.affiliation: 3 Department of Neurology, University of Pittsburgh School of Medicine , the Safar Center for Resuscitation Research and the Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.
authors.forename: Milos D
authors.initials: MD
authors.lastname: Ikonomovic
authors.affiliation: 4 Department of Neurological Surgery, University of Pittsburgh School of Medicine , the Safar Center for Resuscitation Research and the Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.
authors.forename: Ava M
authors.initials: AM
authors.lastname: Puccio
authors.affiliation: 1 Department of Critical Care Medicine, University of Pittsburgh School of Medicine , the Safar Center for Resuscitation Research and the Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.|5 Department of Pediatrics, University of Pittsburgh School of Medicine , the Safar Center for Resuscitation Research and the Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Kochanek
authors.affiliation: 4 Department of Neurological Surgery, University of Pittsburgh School of Medicine , the Safar Center for Resuscitation Research and the Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.
authors.forename: David O
authors.initials: DO
authors.lastname: Okonkwo
authors.affiliation: 1 Department of Critical Care Medicine, University of Pittsburgh School of Medicine , the Safar Center for Resuscitation Research and the Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.|5 Department of Pediatrics, University of Pittsburgh School of Medicine , the Safar Center for Resuscitation Research and the Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.|6 Clinical and Translational Science Institute, University of Pittsburgh School of Medicine , the Safar Center for Resuscitation Research and the Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.
authors.forename: Robert S B
authors.initials: RS
authors.lastname: Clark
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism; D001930:Brain Injuries / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D012720:Severity of Illness Index; D014015:Tissue Banks; D055815:Young Adult
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C513055:ABCB1 protein, human; C421109:multidrug resistance-associated protein 1
keywords: ABCB1; ABCC1; MDR1; MRP1; multidrug resistance protein; multidrug resistance-associated protein; p-glycoprotein