title: Type 2 IP(3) receptors are involved in uranyl acetate induced apoptosis in HEK 293 cells.
abstract: Calcium released from endoplasmic reticulum through special calcium release channels - inositol 1,4,5-trisphosphate receptors (IP(3)Rs) and ryanodine receptors (RyRs) - serves as a main source of cytosolic calcium signaling in the majority of cell types in physiological state and also in pathological situations. In this work, we studied whether IP(3)Rs can be involved in uranyl acetate induced nephrotoxicity. Using human embryonic kidney cell line (HEK293) as an experimental model we have found that uranyl acetate (5 and 50microM) up-regulates both, mRNA and protein levels of the type 1 and type 2 IP(3) receptors in HEK293 cells. This increase was associated with elevated expression of proapoptotic factors Bax and Caspase 3 and also by higher extent of apoptosis. Vice versa, induction of apoptosis resulted in increased mRNA levels of IP(3)R2 and also elevated levels of apoptotic markers. Therefore we propose that enhanced expression of the type 2 IP(3)Rs can at least partially contribute to increased levels of apoptosis due to uranyl acetate treatment.
authors.affiliation: Institute of Virology, Centre of Excellence for Cardiovascular Research, Bratislava, Slovakia.
authors.forename: Juraj
authors.initials: J
authors.lastname: Kopacek
authors.forename: Karol
authors.initials: K
authors.lastname: Ondrias
authors.forename: Barbora
authors.initials: B
authors.lastname: Sedlakova
authors.forename: Jana
authors.initials: J
authors.lastname: Tomaskova
authors.forename: Lucia
authors.initials: L
authors.lastname: Zahradnikova
authors.forename: Jan
authors.initials: J
authors.lastname: Sedlak
authors.forename: Zdena
authors.initials: Z
authors.lastname: Sulova
authors.forename: Alexandra
authors.initials: A
authors.lastname: Zahradnikova
authors.forename: Jaromir
authors.initials: J
authors.lastname: Pastorek
authors.forename: Olga
authors.initials: O
authors.lastname: Krizanova
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000187:drug effects; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000633:toxicity*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D009942:Organometallic Compounds; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; C005460:uranyl acetate; D053148:Caspase 3; D002118:Calcium