title: Aldo-keto reductase family 1, member B10 is secreted through a lysosome-mediated non-classical pathway.
abstract: 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, Ca(2+) and the Ca(2+) carrier ionomycin, lysosomotropic NH(4)Cl, 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.
authors.affiliation: Department of Medical Microbiology, Immunology, & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, 913 N. Rutledge Street, Springfield, IL 62794, USA.
authors.forename: Di-xian
authors.initials: DX
authors.lastname: Luo
authors.forename: Mei C
authors.initials: MC
authors.lastname: Huang
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.forename: Zachary
authors.initials: Z
authors.lastname: Gao
authors.forename: Duan-fang
authors.initials: DF
authors.lastname: Liao
authors.forename: Deliang
authors.initials: D
authors.lastname: Cao
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000449:Aldehyde Reductase / Q000378:metabolism*; D000074408:Aldo-Keto Reductases; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002280:Basal Cell Carcinoma / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism*; D003470:Culture Media / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005089:Exocytosis; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007422:Intestines / Q000166:cytology / Q000201:enzymology; D007668:Kidney / Q000166:cytology / Q000201:enzymology; D008247:Lysosomes / Q000378:metabolism*
chemical_list: D003470:Culture Media; D000255:Adenosine Triphosphate; C120471:AKR1B10 protein, human; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase; D002118:Calcium