title: High glucose increases metallothionein expression in renal proximal tubular epithelial cells.
abstract: Metallothionein (MT) is an intracellular metal-binding, cysteine-rich protein, and is a potent antioxidant that protects cells and tissues from oxidative stress. Although the major isoforms MT-1 and -2 (MT-1/-2) are highly inducible in many tissues, the distribution and role of MT-1/-2 in diabetic nephropathy are poorly understood. In this study, diabetes was induced in adult male rats by streptozotocin, and renal tissues were stained with antibodies for MT-1/-2. MT-1/-2 expression was also evaluated in mProx24 cells, a mouse renal proximal tubular epithelial cell line, stimulated with high glucose medium and pretreated with the antioxidant vitamin E. MT-1/-2 expression was gradually and dramatically increased, mainly in the proximal tubular epithelial cells and to a lesser extent in the podocytes in diabetic rats, but was hardly observed in control rats. MT-1/-2 expression was also increased by high glucose stimulation in mProx24 cells. Because the induction of MT was suppressed by pretreatment with vitamin E, the expression of MT-1/-2 is induced, at least in part, by high glucose-induced oxidative stress. These observations suggest that MT-1/-2 is induced in renal proximal tubular epithelial cells as an antioxidant to protect the kidney from oxidative stress, and may offer a novel therapeutic target against diabetic nephropathy.
authors.affiliation: Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan. daiogawa@md.okayama-u.ac.jp
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ogawa
authors.forename: Masato
authors.initials: M
authors.lastname: Asanuma
authors.forename: Ikuko
authors.initials: I
authors.lastname: Miyazaki
authors.forename: Hiromi
authors.initials: H
authors.lastname: Tachibana
authors.forename: Jun
authors.initials: J
authors.lastname: Wada
authors.forename: Norio
authors.initials: N
authors.lastname: Sogawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sugaya
authors.forename: Shinji
authors.initials: S
authors.lastname: Kitamura
authors.forename: Yohei
authors.initials: Y
authors.lastname: Maeshima
authors.forename: Kenichi
authors.initials: K
authors.lastname: Shikata
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Makino
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002460:Cell Line; D003928:Diabetic Nephropathies / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014810:Vitamin E / Q000494:pharmacology
chemical_list: D000975:Antioxidants; C491054:Mt2 protein, mouse; C491055:Mt2A protein, rat; C525355:metallothionein-1, mouse; D014810:Vitamin E; D008668:Metallothionein; D005947:Glucose