title: Involvement of intracellular glutathione in zinc deficiency-induced activation of hepatic stellate cells.
abstract: Hepatic stellate cells (HSC) play an important role in the development of liver cirrhosis. They are a major source of extracellular matrix and during fibrogenesis undergo an activation process characterized by increased proliferation and collagen synthesis. In this study, we investigated the anti-fibrogenic effect of zinc supplementation on zinc deficiency induced HSC activation. Isolated HSC were incubated with or without zinc chelator, diethylenetriamine penta-acetic acid (DTPA). Type I collagen expression in HSC was detected by immunohistochemistry. The involvement of glutathione (GSH) homeostasis in the anti-fibrogenic action of zinc was also investigated, as GSH is implicated in many cellular events, such as regulation of cell proliferation, remodeling of extracellular matrix and oxidative stress. Intracellular GSH was measured by HPLC. Enhanced type I collagen expression, apoptosis and cell cycle arrest were found in HSC when DTPA was added, but they were inhibited with supplementation with zinc. Zinc deficiency caused a reduction in intracellular GSH 8 h after the addition of DTPA compared with control levels. The results of this study show that in HSC, the chelation of zinc triggers a progression of collagen synthesis and this involves the depletion of intracellular GSH levels after the addition of DTPA.
authors.affiliation: Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan. kojma@life.osaka-cu.ac.jp
authors.forename: Akiko
authors.initials: A
authors.lastname: Kojima-Yuasa
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ohkita
authors.forename: Kumiko
authors.initials: K
authors.lastname: Yukami
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ichikawa
authors.forename: Noriko
authors.initials: N
authors.lastname: Takami
authors.forename: Teruyo
authors.initials: T
authors.lastname: Nakatani
authors.forename: David
authors.initials: D
authors.lastname: Opare Kennedy
authors.forename: Shuhei
authors.initials: S
authors.lastname: Nishiguchi
authors.forename: Isao
authors.initials: I
authors.lastname: Matsui-Yuasa
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis; D005978:Glutathione / Q000032:analysis / Q000502:physiology*; D007124:Immunoenzyme Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011073:Polyamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015032:Zinc / Q000172:deficiency / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D011073:Polyamines; C005391:diethylenetriamine; D005978:Glutathione; D015032:Zinc