AKR1B10 (aldo-keto reductase family 1, member B10) protein is primarily expressed in normal human small intestine and colon, but overexpressed in several types of human cancers and considered as a tumour marker. In the present study, we found that AKR1B10 protein is secreted from normal intestinal epithelium and cultured cancer cells, as detected by a newly developed sandwich ELISA and Western blotting. The secretion of AKR1B10 was not affected by the protein-synthesis inhibitor cycloheximide and the classical protein-secretion pathway inhibitor brefeldin A, but was stimulated by temperature, ATP, Ca2+ and the Ca2+ carrier ionomycin, lysosomotropic NH4Cl, the G-protein activator GTPγS and the G-protein coupling receptor N-formylmethionyl-leucyl-phenylalanine. The ADP-ribosylation factor inhibitor 2-(4-fluorobenzoylamino)-benzoic acid methyl ester and the phospholipase C inhibitor U73122 inhibited the secretion of AKR1B10. In cultured cells, AKR1B10 was present in lysosomes and was secreted with cathepsin D, a lysosomal marker. In the intestine, AKR1B10 was specifically expressed in mature epithelial cells and secreted into the lumen at 188.6–535.7 ng/ml of ileal fluids (mean=298.1 ng/ml, n=11). Taken together, our results demonstrate that AKR1B10 is a new secretory protein belonging to a lysosome-mediated non-classical protein-secretion pathway and is a potential serum marker.
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Research Article|
July 27 2011
Aldo-keto reductase family 1, member B10 is secreted through a lysosome-mediated non-classical pathway
Di-xian Luo;
Di-xian Luo
*Department of Medical Microbiology, Immunology, & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, 913 N. Rutledge Street, Springfield, IL 62794, U.S.A.
†Institute of Pharmacy and Pharmacology, College of Pharmacy and Life Science, University of South China, Hengyang 421001, China
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Mei C. Huang;
Mei C. Huang
‡Department of Internal Medicine, Division of Gastroenterology, Memorial Medical Center, 751 N. Rutledge Street, Springfield, IL 62781, U.S.A.
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Jun Ma;
Jun Ma
*Department of Medical Microbiology, Immunology, & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, 913 N. Rutledge Street, Springfield, IL 62794, U.S.A.
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Zachary Gao;
Zachary Gao
*Department of Medical Microbiology, Immunology, & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, 913 N. Rutledge Street, Springfield, IL 62794, U.S.A.
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Duan-fang Liao;
Duan-fang Liao
1
†Institute of Pharmacy and Pharmacology, College of Pharmacy and Life Science, University of South China, Hengyang 421001, China
§Department of Traditional Chinese Diagnostics, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 420108, China
1Correspondence may be addressed to either of these authors (email dcao@siumed.edu or dfliao66@yahoo.com.cn).
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Deliang Cao
Deliang Cao
1
*Department of Medical Microbiology, Immunology, & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, 913 N. Rutledge Street, Springfield, IL 62794, U.S.A.
1Correspondence may be addressed to either of these authors (email dcao@siumed.edu or dfliao66@yahoo.com.cn).
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Publisher: Portland Press Ltd
Received:
January 17 2011
Revision Received:
May 14 2011
Accepted:
May 18 2011
Accepted Manuscript online:
May 18 2011
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem J (2011) 438 (1): 71–80.
Article history
Received:
January 17 2011
Revision Received:
May 14 2011
Accepted:
May 18 2011
Accepted Manuscript online:
May 18 2011
Citation
Di-xian Luo, Mei C. Huang, Jun Ma, Zachary Gao, Duan-fang Liao, Deliang Cao; Aldo-keto reductase family 1, member B10 is secreted through a lysosome-mediated non-classical pathway. Biochem J 15 August 2011; 438 (1): 71–80. doi: https://doi.org/10.1042/BJ20110111
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