siRNA-mediated AMPKalpha1 subunit gene PRKAA1 silencing enhances methylmercury toxicity in HEK293 cells.
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.
Hwang
Gi-Wook
GW
Laboratory of Molecular and Biochemical Toxicology, Department of Microbiology, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
Tobita
Mayumi
M
Takahashi
Tsutomu
T
Kuge
Shusuke
S
Kita
Kayoko
K
Naganuma
Akira
A
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
D008767:Methylmercury Compounds; D034741:RNA, Small Interfering; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human; C031143:AICA ribonucleotide