title: Involvement of c-Met- and phosphatidylinositol 3-kinase dependent pathways in arsenite-induced downregulation of catalase in hepatoma cells.
abstract: Catalase protects cells from reactive oxygen species-induced damage by catalyzing the breakdown of hydrogen peroxide to oxygen and water. Arsenite decreases catalase activity; it activates phosphatidylinositol 3-kinase (PI3K) and its key downstream effector Akt in a variety of cells. The PI3K pathway is known to inhibit catalase expression. c-Met, an upstream regulator of PI3K and Akt, is also involved in the regulation of catalase expression. To examine the involvement of c-Met and PI3K pathways in the arsenite-induced downregulation of catalase, catalase mRNA and protein expression were analyzed in the human hepatoma cell line HepG2 treated with arsenite and either an inhibitor of c-Met (PHA665752 (PHA)) or of PI3K (LY294002 (LY)). Arsenite treatment markedly activated Akt and decreased the levels of both catalase mRNA and protein. Both PHA and LY attenuated arsenite-induced activation of Akt. PHA and LY treatment also prevented the inhibitory effect of arsenite on catalase protein expression but did not affect the level of catalase mRNA. These findings suggest that arsenite-induced inhibition of catalase expression is regulated at the mRNA and post-transcriptional levels in HepG2 cells, and that the post-transcriptional regulation is mediated via c-Met- and PI3K-dependent mechanisms.
authors: College of Veterinary Medicine, Seoul National University, Seoul, Korea.
authors: Soohee
authors: S
authors: Kim
authors: Seung Heon
authors: SH
authors: Lee
authors: Sukmo
authors: S
authors: Kang
authors: Lyon
authors: L
authors: Lee
authors: Jung-Duck
authors: JD
authors: Park
authors: Doug-Young
authors: DY
authors: Ryu
mesh_terms: D018053:Arsenites / Q000494:pharmacology*; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D002867:Chromones / Q000494:pharmacology; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects* / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D056945:Hep G2 Cells; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D009025:Morpholines / Q000494:pharmacology; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013450:Sulfones / Q000494:pharmacology
chemical_list: C480541:5-((2,6-dichlorobenzyl)sulfonyl)-3-((3,5-dimethyl-4-((2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl)carbonyl)-1H-pyrrol-2-yl)methylene)-1,3-dihydro-2H-indol-2-one; D018053:Arsenites; D002867:Chromones; D007211:Indoles; D009025:Morpholines; D012333:RNA, Messenger; D013450:Sulfones; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D002374:Catalase; D058539:Phosphatidylinositol 3-Kinase; D019859:Proto-Oncogene Proteins c-met; D051057:Proto-Oncogene Proteins c-akt; C015001:arsenite