Alpha-tocopherol induces calnexin in renal tubular cells: another protective mechanism against free radical-induced cellular damage.

Abstract

Pre-administration of alpha-tocopherol is protective against oxidative renal tubular damage and subsequent carcinogenesis by ferric nitrilotriacetate (Fe-NTA) in rats. We searched for mechanisms other than the scavenging effect of alpha-tocopherol with microarray analyses, which implicated calnexin, a chaperone for glycoproteins. Renal mRNA levels of calnexin significantly increased 3h after an injection of Fe-NTA in rats fed a standard diet whereas those fed an alpha-tocopherol-supplemented diet showed an increase prior to injection, but after injection showed a decrease in renal calnexin mRNA levels, with unaltered protein levels. In experiments using LLC-PK1 cells, addition of alpha-tocopherol was protective against oxidative stress by H2O2, concomitant with calnexin induction. Knockdown of calnexin by siRNA significantly reduced this protection. Furthermore, COS-7 cells transfected with the calnexin gene were more resistant to H2O2. Together with the fact that alpha-tocopherol induced N-acetylglucosaminyltransferase 3, our data suggest that alpha-tocopherol modifies glycoprotein metabolism partially by conferring mild ER stress. This adds another molecular mechanism of alpha-tocopherol toward cancer prevention.

• Authors: Wen-Hua Lee, Shinya Akatsuka, Tomoyuki Shirase, Khokon Kumar Dutta, Li Jiang, Yu-Ting Liu, Janice Onuki, Yoshihiro Yamada, Katsuya Okawa, Youichiro Wada, Akira Watanabe, Takahide Kohro, Noriko Noguchi, Shinya Toyokuni
• Journal: Archives of biochemistry and biophysics (Arch Biochem Biophys) Vol. 453 Issue 2 Pg. 168-78 (Sep 15 2006) ISSN: 0003-9861 [Print] United States
• PMID: 16908007 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carcinogens
• Ferric Compounds
• Free Radicals
• Calnexin
• alpha-Tocopherol
• Nitrilotriacetic Acid
• ferric nitrilotriacetate

Topics

• Animals
• Calnexin
• Carcinogens (toxicity)
• Cells, Cultured
• Cytoprotection (drug effects)
• Dose-Response Relationship, Drug
• Ferric Compounds (toxicity)
• Free Radicals (toxicity)
• Kidney Neoplasms (metabolism, pathology, prevention & control)
• Kidney Tubules (drug effects, metabolism, pathology)
• Male
• Nitrilotriacetic Acid (analogs & derivatives, toxicity)
• Oxidative Stress (drug effects)
• Precancerous Conditions (chemically induced, metabolism)
• Rats
• Rats, Wistar
• alpha-Tocopherol (administration & dosage)