4.2 Article

Expression of ABC-type transport proteins in human platelets

Journal

PHARMACOGENETICS AND GENOMICS
Volume 20, Issue 6, Pages 396-400

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FPC.0b013e32833997b0

Keywords

ATP-binding cassette transporter; liquid chromatography/mass spectrometry/mass spectrometry; membrane proteins; platelets; TaqMan low-density array; targeted proteomics

Funding

  1. Deutsche Forschungsgemeinschaft (DFG) [SFB-TR19]
  2. German Federal Ministry for Education and Research (BMBF) [03IP612]

Ask authors/readers for more resources

We have identified the ATP-binding cassette (ABC) transporter ABCC4 as an active constituent of mediator-storing granules in human platelets. In addition to multidrug resistance protein 4, other ABC-type transport proteins may contribute to platelet secretory function as well as determine intended or adverse effects of drugs. Here, we provide a comprehensive expression profiling of ABC transporters in human platelets based on a novel screening approach by combining the TaqMan low-density array RNA screening platform with a recently developed liquid chromatography/mass spectrometry (MS)/MS method for the simultaneous detection of membrane proteins. Transcripts of 25 ABC transporters were detected and showed differential expression compared with megakaryocytic progenitor cells. On the protein level ABCA7, ABCB4, ABCC1, ABCC3 and ABCC4 were identified by liquid chromatography/MS/MS and localized by immunofluorescence microscopy. Their functions may be related to glutathione and lipid homeostasis, secretion of lipid mediators, cell protection as well as drug transport. Pharmacogenetics and Genomics 20: 396-400 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.2
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Cell Biology

Human platelets display dysregulated sepsis-associated autophagy, induced by altered LC3 protein-protein interaction of the Vici-protein EPG5

Hansjorg Schwertz, Jesse W. Rowley, Irina Portier, Elizabeth A. Middleton, Neal D. Tolley, Robert A. Campbell, Alicia S. Eustes, Karin Chen, Matthew T. Rondina

Summary: Platelets play a central role in host responses during sepsis, and abnormalities in autophagic functions in platelets during sepsis are partly due to reduced EPG5-LC3 interactions, regulated by TLR4 engagement, leading to the accumulation of autophagosomes.

AUTOPHAGY (2022)

Article Biochemistry & Molecular Biology

Activation of Annexin A2 signaling at the blood-brain barrier in a mouse model of multiple sclerosis

Kenta Tezuka, Masayoshi Suzuki, Risa Sato, Shohei Kawarada, Tetsuya Terasaki, Yasuo Uchida

Summary: Blood-brain barrier (BBB) dysfunction is a fundamental cause of multiple sclerosis. In this study, protein expression at the BBB of experimental autoimmune encephalomyelitis (EAE) mice was comprehensively quantified using the SWATH method. The down-regulation of tight junction molecules and the up-regulation of molecules involved in cell infiltration and tight junction disruption, including ANXA2, were observed. Interestingly, daily administration of an ANXA2 inhibitor significantly suppressed the development of EAE in mice. These findings suggest that ANXA2 signaling plays an important role in the pathogenesis of EAE.

JOURNAL OF NEUROCHEMISTRY (2022)

Article Chemistry, Medicinal

Knockdown of Podocalyxin Post-Transcriptionally Induces the Expression and Activity of ABCB1/MDR1 in Human Brain Microvascular Endothelial Cells

Hinako Nagano, Seiryo Ogata, Shingo Ito, Takeshi Masuda, Sumio Ohtsuki

Summary: This study reveals the role of Podocalyxin (PODXL) in blood-brain barrier function. PODXL knockdown affects immune response and intracellular trafficking, and regulates the protein expression and efflux activity of ABCB1/MDR1.

JOURNAL OF PHARMACEUTICAL SCIENCES (2022)

Article Chemistry, Multidisciplinary

Effect of Insulin Receptor-Knockdown on the Expression Levels of Blood-Brain Barrier Functional Proteins in Human Brain Microvascular Endothelial Cells

Hinako Nagano, Shingo Ito, Takeshi Masuda, Sumio Ohtsuki

Summary: The study suggests that INSR-mediated signaling is involved in regulating the expression of functional proteins at the blood-brain barrier (BBB), contributing to BBB function maintenance. Changes in protein expressions, particularly those related to amyloid-beta peptides, in INSR knockdown cells may contribute to the development of cerebral amyloid angiopathy through the suppression of INSR-mediated signaling.

PHARMACEUTICAL RESEARCH (2022)

Article Oncology

Targeted proteomics for cancer biomarker verification and validation

Seiryo Ogata, Takeshi Masuda, Shingo Ito, Sumio Ohtsuki

Summary: Targeted proteomics is a method that quantifies target proteins using liquid chromatography-tandem mass spectrometry. It allows rapid development, simultaneous measurement of multiple proteins, and high-specificity detection of modifications. It can seamlessly transfer candidate cancer biomarker proteins from discovery to verification and validation, accelerating the cancer biomarker pipeline.

CANCER BIOMARKERS (2022)

Article Biochemistry & Molecular Biology

A human blood-arachnoid barrier atlas of transporters, receptors, enzymes, and tight junction and marker proteins: Comparison with dog and pig in absolute abundance

Yasuo Uchida, Hina Takeuchi, Ryohei Goto, Clemens Braun, Holger Fuchs, Naoki Ishiguro, Masaki Takao, Mitsutoshi Tano, Tetsuya Terasaki

Summary: The purpose of this study was to determine the absolute abundance of proteins at the human blood-arachnoid barrier (BAB) and compare with dogs and pigs. The results showed that there were 52 highly expressed proteins at the BAB in humans, and the differences between humans and dogs or pigs were within 3-fold for most proteins. These findings provide important insights into the physiological roles of the BAB and the differences between humans and animals.

JOURNAL OF NEUROCHEMISTRY (2022)

Article Chemistry, Multidisciplinary

Pharmacoproteomics of Brain Barrier Transporters and Substrate Design for the Brain Targeted Drug Delivery

Kristiina M. Huttunen, Tetsuya Terasaki, Arto Urtti, Ahmed B. Montaser, Yasuo Uchida

Summary: One of the major challenges in CNS-drug development is the presence of barriers that prevent substances from entering the brain. This review discusses the expression profiles of transporters in these barriers and how they affect drug disposition in the brain. It also highlights the advancements in structural biology and computational resources that have improved our understanding of transporter dynamics and aided in the design of transporter-utilizing compounds.

PHARMACEUTICAL RESEARCH (2022)

Article Chemistry, Analytical

Water Droplet-in-Oil Digestion Method for Single-Cell Proteomics

Takeshi Masuda, Yuma Inamori, Arisu Furukawa, Maki Yamahiro, Kazuki Momosaki, Chih-Hsiang Chang, Daiki Kobayashi, Hiroto Ohguchi, Yawara Kawano, Shingo Ito, Norie Araki, Shao-En Ong, Sumio Ohtsuki

Summary: This study presents a water droplet in-oil digestion (WinO) method for proteomic analysis in limited sample amounts. The method increases protein and peptide recovery by minimizing the contact area between the sample solution and the container. It has been successfully applied to single-cell proteomics and shows promise for its wide applicability and suitability.

ANALYTICAL CHEMISTRY (2022)

Article Medicine, Research & Experimental

Human Immortalized Cell-Based Blood-Brain Barrier Spheroid Models Offer an Evaluation Tool for the Brain Penetration Properties of Macromolecules

Keita Kitamura, Ayaka Okamoto, Hanae Morio, Ryuto Isogai, Ryo Ito, Yoshiyuki Yamaura, Saki Izumi, Takafumi Komori, Shingo Ito, Sumio Ohtsuki, Hidetaka Akita, Tomomi Furihata

Summary: This study characterizes the ability of the hiMCS-BBB models to evaluate receptor-mediated transcytosis (RMT)-mediated blood-brain barrier (BBB) penetration properties of middle/macromolecules. The results show that the hiMCS-BBB models have the potential to provide valuable tools for exploring and identifying middle/macromolecules with excellent BBB permeability levels.

MOLECULAR PHARMACEUTICS (2022)

Article Biochemistry & Molecular Biology

Tumor cell-derived ANGPTL2 promotes β-catenin-driven intestinal tumorigenesis

Haruki Horiguchi, Tsuyoshi Kadomatsu, Shinsei Yumoto, Takeshi Masuda, Keishi Miyata, Shuji Yamamura, Michio Sato, Jun Morinaga, Sumio Ohtsuki, Hideo Baba, Toshiro Moroishi, Yuichi Oike

Summary: Tumor cell-derived ANGPTL2 promotes beta-catenin-driven intestinal tumorigenesis by upregulating OB-cadherin expression and blocking destruction complex-independent proteasomal degradation of beta-catenin proteins. It also leads to decreased cell surface integrin alpha 5 beta 1 expression.

ONCOGENE (2022)

Article Pharmacology & Pharmacy

Proteomics-Based Transporter Identification by the PICK Method: Involvement of TM7SF3 and LHFPL6 in Proton-Coupled Organic Cation Antiport at the Blood-Brain Barrier

Toshiki Kurosawa, Yuma Tega, Yasuo Uchida, Kei Higuchi, Hidetsugu Tabata, Takaaki Sumiyoshi, Yoshiyuki Kubo, Tetsuya Terasaki, Yoshiharu Deguchi

Summary: The PICK method successfully identified TM7SF3 and LHFPL6 as candidate proteins for the H+/OC antiporter and their functional analysis confirmed their role as components of this antiporter.

PHARMACEUTICS (2022)

Article Chemistry, Multidisciplinary

Human Hepatic Transporter Signature Peptides for Quantitative Targeted Absolute Proteomics: Selection, Digestion Efficiency, and Peptide Stability

Ayano Mori, Takeshi Masuda, Shingo Ito, Sumio Ohtsuki

Summary: This study comprehensively assessed the digestion efficiency and stability of tryptic peptides, identified optimal signature peptides for human hepatic transporters and membrane marker proteins, and provided reliable quantification of human hepatic transporters for integrated pharmacokinetic studies.

PHARMACEUTICAL RESEARCH (2022)

Article Biotechnology & Applied Microbiology

Influence of MDR1 gene polymorphism (2677G>T) on expression and function of P-glycoprotein at the blood-brain barrier: utilizing novel P-glycoprotein humanized mice with mutation

Yuki Yamasaki, Takashi Moriwaki, Seiryo Ogata, Shingo Ito, Sumio Ohtsuki, Genki Minegishi, Satoshi Abe, Yumi Ohta, Kanako Kazuki, Kaoru Kobayashi, Yasuhiro Kazuki

Summary: This study developed a novel P-glycoprotein humanized mouse line carrying the 2677G>T mutation and evaluated its influence on the expression and function of P-glycoprotein at the blood-brain barrier. The results showed that the mutation did not alter the expression levels of P-glycoprotein but increased the brain penetration of P-glycoprotein substrates. This mutant mouse line provides a useful model for studying the impact of MDR1 gene mutations on P-glycoprotein at the blood-brain barrier.

PHARMACOGENETICS AND GENOMICS (2022)

Article Hematology

Autophagy and its consequences for platelet biology

Hansjorg Schwertz, Elizabeth A. Middleton

Summary: Autophagy plays an important role in megakaryopoiesis and platelet function, contributing to cellular function and homeostasis. Autophagy in platelets is involved in platelet function and clinical implications, but further research is needed to fully understand its role.

THROMBOSIS RESEARCH (2023)

Article Cell Biology

SETD1A regulates transcriptional pause release of heme biosynthesis genes in leukemia

Takayuki Hoshii, Sarah Perlee, Sota Kikuchi, Bahityar Rahmutulla, Masaki Fukuyo, Takeshi Masuda, Sumio Ohtsuki, Tomoyoshi Soga, Behnam Nabet, Atsushi Kaneda

Summary: The protein degrader technology was used in this study to degrade SETD1A and investigate its role in acute myeloid leukemia (AML) cells. The results showed that SETD1A degradation led to downregulation of DNA repair and heme biosynthesis pathways, and SETD1A was also found to be essential for maintaining mitochondrial respiration in AML cells. Furthermore, the study revealed a non-enzymatic role of SETD1A in transcriptional pause release, providing insight into the mechanism of RNA polymerase II (RNAPII) pausing and its function in cancer.

CELL REPORTS (2022)

No Data Available