title: siRNA-mediated AMPKalpha1 subunit gene PRKAA1 silencing enhances methylmercury toxicity in HEK293 cells.
abstract: The environmental pollutant methylmercury is a potent neurotoxin. The mechanisms of toxicity and biological defense remain largely unknown. We found that inhibiting the expression of PRKAA1 (AMPKalpha1), an activated subunit of AMP-activated protein kinase (AMPK), increased susceptibility of HEK293 cells to methylmercury toxicity. Treatment of the cells with AICAR (5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside), an AMPK activator, reduced the methylmercury toxicity. Here, we suggest for the first time that the activation (phosphorylation) of AMPK may play an important role in reducing the toxicity of methylmercury.
authors.affiliation: Laboratory of Molecular and Biochemical Toxicology, Department of Microbiology, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
authors.forename: Gi-Wook
authors.initials: GW
authors.lastname: Hwang
authors.forename: Mayumi
authors.initials: M
authors.lastname: Tobita
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takahashi
authors.forename: Shusuke
authors.initials: S
authors.lastname: Kuge
authors.forename: Kayoko
authors.initials: K
authors.lastname: Kita
authors.forename: Akira
authors.initials: A
authors.lastname: Naganuma
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D008767:Methylmercury Compounds / Q000633:toxicity*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism*; D012265:Ribonucleotides / Q000494:pharmacology; D015398:Signal Transduction / Q000235:genetics
chemical_list: D008767:Methylmercury Compounds; D034741:RNA, Small Interfering; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human; C031143:AICA ribonucleotide