title: Regulation of SNARK activity in response to cellular stresses.
abstract: SNARK is a member of the AMPK subfamily of serine/threonine protein kinases. In this study, we examined the regulation of SNARK activity in kidney (BHK, HEK293), pancreatic beta-cell insulinoma (INS-1), hepatocarcinoma (H4IIE) and keratinocyte (NRKC)-derived cell lines in response to diverse cellular stresses. We show that SNARK activity is regulated by glucose- or glutamine-deprivation, induction of endoplasmic reticulum stress by homocysteine or DTT, elevation of cellular AMP and/or depletion of ATP, hyperosmotic stress, salt stress, ultraviolet B radiation and oxidative stress caused by hydrogen peroxide. Moreover, the regulation of SNARK activity in response to cellular stresses depends greatly upon cell type. Furthermore, SNARK activity is downregulated by metformin in a dose- and time-dependent manner in H4IIE cells. These observations support a role for SNARK as a molecular component of the cellular stress response.
authors.affiliation: Department of Medicine, Division of Dermatology, University of Toronto, Toronto General Hospital, Banting Institute, Room 317, 100 College Street, Toronto, Ontario, Canada.
authors.forename: Diana L
authors.initials: DL
authors.lastname: Lefebvre
authors.forename: Cheryl F
authors.initials: CF
authors.lastname: Rosen
mesh_terms: D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D004229:Dithiothreitol / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects; D015870:Gene Expression; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006710:Homocysteine / Q000494:pharmacology; D006801:Humans; D006982:Hypertonic Solutions / Q000494:pharmacology; D008687:Metformin / Q000494:pharmacology; D009997:Osmotic Pressure; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D014018:Tissue Distribution; D014466:Ultraviolet Rays
chemical_list: D006982:Hypertonic Solutions; D006710:Homocysteine; D005973:Glutamine; D000249:Adenosine Monophosphate; D008687:Metformin; C426226:Nuak2 protein, rat; D017346:Protein Serine-Threonine Kinases; D005947:Glucose; D004229:Dithiothreitol