title: Nanosecond pulsed electric fields activate AMP-activated protein kinase: implications for calcium-mediated activation of cellular signaling.
abstract: Nanosecond pulsed electric fields (nsPEFs) are increasingly being recognized as a potential tool for use in the life sciences. Exposure of human cells to nsPEFs elicits the formation of small membrane pores, intracellular Ca(2+) mobilization, signaling pathway activation, and apoptosis. Here we report the activation of AMP-activated protein kinase (AMPK) by nsPEFs. AMPK activation is generally achieved by the phosphorylation of AMPK in response to changes in cellular energy status and is mediated by two protein kinases, LKB1 and CaMKK. Exposure to nsPEFs rapidly induced phosphorylation of AMPK and its downstream target ACC in both LKB1-proficient and LKB1-deficient cells. In LKB1-deficient cells, AMPK activation by nsPEFs was mediated by CaMKK and required extracellular Ca(2+), which suggested the occurrence of Ca(2+) mobilization and its participation in AMPK activation by nsPEFs. Our results provide experimental evidence for a direct link between activated cellular signaling and Ca(2+) mobilization in nsPEF-exposed cells.
authors.affiliation: Bioelectrics Research Center, Kumamoto University, Kumamoto 860-8555, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Morotomi-Yano
authors.forename: Hidenori
authors.initials: H
authors.lastname: Akiyama
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Yano
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases / Q000096:biosynthesis*; D002118:Calcium / Q000378:metabolism*; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000378:metabolism; D004574:Electromagnetic Fields; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases; D002118:Calcium