title: Osmolarity and glucose differentially regulate aldose reductase activity in cultured mouse podocytes.
abstract: Podocyte injury is associated with progression of many renal diseases, including diabetic nephropathy. In this study we examined whether aldose reductase (AR), the enzyme implicated in diabetic complications in different tissues, is modulated by high glucose and osmolarity in podocyte cells. AR mRNA, protein expression, and activity were measured in mouse podocytes cultured in both normal and high glucose and osmolarity for 6 hours to 5 days. Hyperosmolarity acutely stimulated AR expression and activity, with subsequent increase of AR expression but decrease of activity. High glucose also elevated AR protein level; however, this was not accompanied by respective enzyme activation. Furthermore, high glucose appeared to counteract the osmolarity-dependent activation of AR. In conclusion, in podocytes AR is modulated by high glucose and increased osmolarity in a different manner. Posttranslational events may affect AR activity independent of enzyme protein amount. Activation of AR in podocytes may be implicated in diabetic podocytopathy.
authors.affiliation: Department of Pathophysiology, Medical University of Gdansk, Poland. blew@gumed.edu.pl
authors.forename: Barbara
authors.initials: B
authors.lastname: Lewko
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Latawiec
authors.forename: Anna
authors.initials: A
authors.lastname: Maryn
authors.forename: Anna
authors.initials: A
authors.lastname: Barczyńska
authors.forename: Michał
authors.initials: M
authors.lastname: Pikuła
authors.forename: Maciej
authors.initials: M
authors.lastname: Zieliński
authors.forename: Apolonia
authors.initials: A
authors.lastname: Rybczyńska
mesh_terms: D000449:Aldehyde Reductase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003928:Diabetic Nephropathies / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D009994:Osmolar Concentration; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D013997:Time Factors
chemical_list: D000449:Aldehyde Reductase; D005947:Glucose