Type 2 IP(3) receptors are involved in uranyl acetate induced apoptosis in HEK 293 cells.
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.
Kopacek
Juraj
J
Institute of Virology, Centre of Excellence for Cardiovascular Research, Bratislava, Slovakia.
Ondrias
Karol
K
Sedlakova
Barbora
B
Tomaskova
Jana
J
Zahradnikova
Lucia
L
Sedlak
Jan
J
Sulova
Zdena
Z
Zahradnikova
Alexandra
A
Pastorek
Jaromir
J
Krizanova
Olga
O
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
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