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Toni Schumacher, Ralf A Benndorf
Adenosine triphosphate (ATP)-binding cassette (ABC) transporters may play an important role in the pathogenesis of atherosclerotic vascular diseases due to their involvement in cholesterol homeostasis, blood pressure regulation, endothelial function, vascular inflammation, as well as platelet production and aggregation. In this regard, ABC transporters, such as ABCA1, ABCG5 and ABCG8, were initially found to be responsible for genetically-inherited syndromes like Tangier diseases and sitosterolemia. These findings led to the understanding of those transporter's function in cellular cholesterol efflux and thereby also linked them to atherosclerosis and cardiovascular diseases (CVD)...
April 6, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Savitha Varatharajan, Ajay Abraham, Sreeja Karathedath, Sukanya Ganesan, Kavitha M Lakshmi, Nancy Arthur, Vivi M Srivastava, Biju George, Alok Srivastava, Vikram Mathews, Poonkuzhali Balasubramanian
INTRODUCTION: Drug resistance and relapse are considered to be the major reasons for treatment failure in acute myeloid leukemia (AML). There is limited data on the role of ABC transporter expression on in vitro sensitivity to cytarabine (Ara-C) and daunorubicin (Dnr) in primary AML cells. PATIENTS & METHODS: RNA expression levels of 12 ABC transporters were analyzed by real-time quantitative PCR in 233 de novo adult acute myeloid leukemia patients. Based on cytarabine or Dnr IC50, the samples were categorized as sensitive, intermediate and resistant...
February 2017: Pharmacogenomics
Taku Nakayama, Shimpei Otsuka, Tatsuya Kobayashi, Hodaka Okajima, Kentaro Matsumoto, Yuichiro Hagiya, Keiji Inoue, Taro Shuin, Motowo Nakajima, Tohru Tanaka, Shun-Ichiro Ogura
Photodynamic therapy (PDT) and diagnosis (PDD) using 5-aminolevulinic acid (ALA) to drive the production of an intracellular photosensitizer, protoporphyrin IX (PpIX), are in common clinical use. However, the tendency to accumulate PpIX is not well understood. Patients with cancer can develop recurrent metastatic disease with latency periods. This pause can be explained by cancer dormancy. Here we created uniformly sized PC-3 prostate cancer spheroids using a 3D culture plate (EZSPHERE). We demonstrated that cancer cells exhibited dormancy in a cell density-dependent manner not only in spheroids but also in 2D culture...
November 18, 2016: Scientific Reports
Immacolata Andolfo, Roberta Russo, Antonella Gambale, Achille Iolascon
After the first proposed model of the red blood cell membrane skeleton 36 years ago, several additional proteins have been discovered during the intervening years, and their relationship with the pathogenesis of the related disorders have been somewhat defined. The knowledge of erythrocyte membrane structure is important because it represents the model for spectrin-based membrane skeletons in all cells and because defects in its structure underlie multiple hemolytic anemias. This review summarizes the main features of erythrocyte membrane disorders, dividing them into structural and altered permeability defects, focusing particularly on the most recent advances...
November 2016: Haematologica
J Zhang, R Cheng, J Liang, C Ni, M Li, Z Yao
Pathogenic mutations in genes (SASH1 and PTPN11) can cause a rare genetic disorder associated with pigmentation defects and the well-known LEOPARD syndrome, respectively. Both conditions presented with lentiginous phenotypes. The aim of this study was to arrive at definite diagnoses of three Chinese boys with clinically suspected lentigines-related syndromes. ADAR1, ABCB6, SASH1 and PTPN11 were candidate genes for mutational screening. Sanger sequencing was performed to identify the mutations, whereas bioinformatic analysis was used to predict the pathogenicity of novel missense mutations...
October 2016: Clinical Genetics
Yu Fukuda, Pak Leng Cheong, John Lynch, Cheryl Brighton, Sharon Frase, Vasileios Kargas, Evadnie Rampersaud, Yao Wang, Vijay G Sankaran, Bing Yu, Paul A Ney, Mitchell J Weiss, Peter Vogel, Peter J Bond, Robert C Ford, Ronald J Trent, John D Schuetz
Hereditary porphyrias are caused by mutations in genes that encode haem biosynthetic enzymes with resultant buildup of cytotoxic metabolic porphyrin intermediates. A long-standing open question is why the same causal porphyria mutations exhibit widely variable penetrance and expressivity in different individuals. Here we show that severely affected porphyria patients harbour variant alleles in the ABCB6 gene, also known as Lan, which encodes an ATP-binding cassette (ABC) transporter. Plasma membrane ABCB6 exports a variety of disease-related porphyrins...
2016: Nature Communications
Jacek Grebowski, Maciej Studzian, Grzegorz Bartosz, Lukasz Pulaski
The need for large amounts of reproducibly produced and isolated protein arises not only in structural studies, but even more so in biochemical ones, and with regard to ABC transporters it is especially pressing when faced with the prospect of enzymatic/transport activity studies, substrate screening etc. Thus, reliable heterologous expression systems/model organisms for large and complex proteins are at a premium. We have verified the applicability of the recently established novel eukaryotic expression system, using Leishmania tarentolae as a host, for human ABC protein overexpression...
November 2016: Biochimica et Biophysica Acta
Immacolata Andolfo, Roberta Russo, Francesco Manna, Gianluca De Rosa, Antonella Gambale, Soha Zouwail, Nicola Detta, Catia Lo Pardo, Seth L Alper, Carlo Brugnara, Alok K Sharma, Lucia De Franceschi, Achille Iolascon
Isolated familial pseudohyperkalemia is a dominant red cell trait characterized by cold-induced 'passive leak' of red cell potassium ions into plasma. The causative gene of this condition is ABCB6, which encodes an erythrocyte membrane ABC transporter protein bearing the Langereis blood group antigen system. In this study analyzing three new families, we report the first functional characterization of ABCB6 mutants, including the homozygous mutation V454A, heterozygous mutation R276W, and compound heterozygous mutations R276W and R723Q (in trans)...
August 2016: Haematologica
N S Jayanthi, V Anandan, W Afthab Jameela, V Senthil Kumar, P Lavanya
Dyschromatosis Universalis Hereditaria (DUH) belongs to a group of congenital diffuse reticulate pigmentary disorders characterised by both hypo and hyper pigmented macules. It is both hereditary and sporadic. A number of associated cutaneous and systemic diseases have been reported. The recent discovery of the mutation in ATP binding cassette protein, ABCB6 in DUH attempts to explain the reason behind the pigmentary abnormalities and varied associations. We add a new association by reporting a case of DUH with primary ovarian failure (POF) and hypothyroidism...
March 2016: Journal of Clinical and Diagnostic Research: JCDR
Carlo Mangia, Alice Vismarra, Laura Kramer, Lesley Bell-Sakyi, Daniele Porretta, Domenico Otranto, Sara Epis, Giulio Grandi
BACKGROUND: Ticks are among the most important vectors of pathogens causing human and animal disease. Acaricides are used to control tick infestation, although there are increasing reports of resistance. Recently, over-expression of ATP-binding cassette (ABC) transporter proteins (P-glycoproteins, PgP) has been implicated in resistance to the acaricide ivermectin in the ticks Rhipicephalus (Boophilus) microplus and Rhipicephalus sanguineus sensu lato. Ixodid tick cell lines have been used to investigate drug resistance mechanisms...
April 18, 2016: Parasites & Vectors
Jia-Wei Liu, Jun Sun, Sergio Vano-Galvan, Feng-Xia Liu, Xiu-Xiu Wei, Dong-Lai Ma
BACKGROUND: The dyschromatoses are a group of disorders characterized by simultaneous hyperpigmented macules together with hypopigmented macules. Dyschromatosis universalis hereditaria (DUH) and dyschromatosis symmetrica hereditaria are two major types. While clinical and histological presentations are similar in these two diseases, genetic diagnosis is critical in the differential diagnosis of these entities. METHODS: Three patients initially diagnosed with DUH were included...
January 5, 2016: Chinese Medical Journal
Omer F Karatas, Esra Guzel, Mehmet B Duz, Michael Ittmann, Mustafa Ozen
BACKGROUND: Prostate cancer (PCa) is the most commonly diagnosed neoplasm and the second leading cause of cancer-related death among men in developed countries. There is no clear evidence showing the success of current screening tests in reducing mortality of PCa. In this study, we aimed to profile expressions of nine ABC transporters, ABCA5, ABCB1, ABCB6, ABCC1, ABCC2, ABCC3, ABCC5, ABCC10, and ABCF2, in recurrent, non-recurrent PCa and normal prostate tissues. METHODS: A total of 77 (39 recurrent, 38 non-recurrent) radical prostatectomy and 20 normal prostate samples, obtained from Baylor College of Medicine Prostate Cancer program, were included into the study and divided into two independent groups as test and validation sample sets...
April 2016: Prostate
Nian-Kang Sun, Shang-Lang Huang, Hsing-Pang Lu, Ting-Chang Chang, Chuck C-K Chao
A systematic analysis of the genes involved in taxol resistance (txr) has never been performed. In the present study, we created txr ovarian carcinoma cell lines to identify the genes involved in chemoresistance. Transcriptome analysis revealed 1,194 overexpressed genes in txr cells. Among the upregulated genes, more than 12 cryptic transcription factors were identified using MetaCore analysis (including AR, C/EBPβ, ERα, HNF4α, c-Jun/AP-1, c-Myc, and SP-1). Notably, individual silencing of these transcription factors (except HNF4`)sensitized txr cells to taxol...
September 29, 2015: Oncotarget
Stancy Joseph, Tamara J Nicolson, George Hammons, Beverly Word, Bridgett Green-Knox, Beverly Lyn-Cook
BACKGROUND: Differences in expression of drug transporters in human kidney contribute to changes in pharmacokinetics and toxicokinetics of a variety of drug compounds. The basal expression levels of genes involved in drug transport processes in the kidney introduces differences in bioavailability, distribution, and clearance of drugs, possibly influencing drug efficacy and adverse reactions. Sex differences in gene expression of transporters are a key cause of differences in sex-dependent pharmacokinetics, which may characterize many drugs and contribute to individual differences in drug efficacy and toxicity...
2015: Biology of Sex Differences
Katalin Kiss, Nora Kucsma, Anna Brozik, Gabor E Tusnady, Ptissam Bergam, Guillaume van Niel, Gergely Szakacs
ATP-binding cassette, subfamily B (ABCB) 6 is a homodimeric ATP-binding cassette (ABC) transporter present in the plasma membrane and in the intracellular organelles. The intracellular localization of ABCB6 has been a matter of debate, as it has been suggested to reside in the mitochondria and the endo-lysosomal system. Using a variety of imaging modalities, including confocal microscopy and EM, we confirm the endo-lysosomal localization of ABCB6 and show that the protein is internalized from the plasma membrane through endocytosis, to be distributed to multivesicular bodies and lysosomes...
April 1, 2015: Biochemical Journal
Hemantkumar Chavan, Feng Li, Robert Tessman, Kristen Mickey, Kenneth Dorko, Timothy Schmitt, Sean Kumer, Sumedha Gunewardena, Nilesh Gaikwad, Partha Krishnamurthy
Although endogenous mechanisms that negatively regulate cytochrome P450 (P450) monooxygenases in response to physiological and pathophysiological signals are not well understood, they are thought to result from alterations in the level of endogenous metabolites, involved in maintaining homeostasis. Here we show that homeostatic changes in hepatic metabolite profile in Abcb6 (mitochondrial ATP-binding cassette transporter B6) deficiency results in suppression of a specific subset of hepatic P450 activity. Abcb6 null mice are more susceptible to pentobarbital-induced sleep and zoxazolamine-induced paralysis, secondary to decreased expression and activity of Cyp3a11 and Cyp2b10...
March 20, 2015: Journal of Biological Chemistry
Kentaro Matsumoto, Yuichiro Hagiya, Yoshio Endo, Motowo Nakajima, Masahiro Ishizuka, Tohru Tanaka, Shun-ichiro Ogura
BACKGROUND: Currently, 5-aminolevulinic acid-based photodynamic diagnosis (ALA-PDD) is used to detect tumors during surgery and exploit tumor-specific accumulation of protoporphyrin IX (PpIX) after administration of ALA. In a recent study, we showed that the human ATP-binding cassette transporter ABCG2 plays a key role in the regulation of PpIX as a specific exporter. However, coproporphyrin III (CPIII) was also detected in urine after ALA administration in patients with tumor, indicating the presence of a CPIII transporter...
March 2015: Photodiagnosis and Photodynamic Therapy
Magdalena Koszarska, Nora Kucsma, Katalin Kiss, Gyorgy Varady, Melinda Gera, Geza Antalffy, Hajnalka Andrikovics, Attila Tordai, Maciej Studzian, Dominik Strapagiel, Lukasz Pulaski, Yoshihiko Tani, Balazs Sarkadi, Gergely Szakacs
Lan is a high-incidence blood group antigen expressed in more than 99.9% of the population. Identification of the human ABC transporter ABCB6 as the molecular basis of Lan has opened the way for studies assessing the relation of ABCB6 function and expression to health and disease. To date, 34 ABCB6 sequence variants have been described in association with reduced ABCB6 expression based on the genotyping of stored blood showing weak or no reactivity with anti-Lan antibodies. In the present study we examined the red blood cell (RBC) surface expression of ABCB6 by quantitative flow cytometry in a cohort of 47 healthy individuals...
2014: PloS One
Kentaro Minami, Youhei Kamijo, Yukihiko Nishizawa, Sho Tabata, Fumito Horikuchi, Masatatsu Yamamoto, Kohich Kawahara, Yoshinari Shinsato, Tokushi Tachiwada, Zhe-Sheng Chen, Kazutake Tsujikawa, Masayuki Nakagawa, Naohiko Seki, Shin-Ichi Akiyama, Kazunari Arima, Yasuo Takeda, Tatsuhiko Furukawa
A previously established arsenite-resistant cell line, KAS, is also resistant to a variety of anticancer drugs. In order to understand responsible molecules for the multidrug resistance phenotype of KAS cells, we examined the expressions of ATP-binding cassette (ABC) transporters and found that the ABCB6 and ABCC1/ multidrug resistance protein 1 (ABCC1/MRP1) were increased. ABCC1/MRP1 was not completely responsible for the drug resistance spectrum of KAS cells and several reports have suggested that ABCB6 is related to anticancer drug and metal resistance...
September 2014: Anticancer Research
Xiaohan Yang, Jianguo Yang, Lei Li, Luyang Sun, Xia Yi, Xiao Han, Wenzhe Si, Ruorong Yan, Zhe Chen, Guojia Xie, Wanjin Li, Yongfeng Shang, Jing Liang
ATP-binding cassette (ABC) transporters are implicated in a diverse range of physiological and pathophysiological processes, such as cholesterol and lipid transportation and multidrug resistance. Despite the considerable efforts made in understanding of the cellular function of ABC proteins, the regulation mechanism of this type of protein is still poorly defined. Here we report the identification and functional characterization of a novel ATPase protein, protein associated with ABC transporters (PAAT), in humans...
November 2014: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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