title: Apoptosis induced clustering of IP(3)R1 in nuclei of non-differentiated PC12 cells.
abstract: Inositol 1,4,5-trisphosphate (IP(3)) receptors are emerging as key sites for regulation by pro- and anti-apoptotic factors. Induction of apoptosis for 3 h increased mRNA and protein levels of type 1 IP(3) receptors in non-differentiated (ND), but not in differentiated (D) PC12 cells. Inhibitors of the IP(3) R's calcium release-2-aminoethoxydiphenyl borate (2-APB) and xestospongin-completely prevented Bax and caspase-3 mRNA increase after treatment with the apoptosis inducer set (AIK), and this reinforces the importance of IP(3) R1 in the apoptosis of ND PC12 cells. Apoptosis induction not only increases the IP(3) R1 protein, but it also causes formation of IP(3) R1 clusters in the nucleus which most likely result from fusion of the nucleoplasmic reticulum and/or IP(3) R1 translocation to the nucleus. This is quite similar to the observations noted after overexpression of IP(3) R1 in PC12 cells. The amount of IP(3) induced calcium release was higher in control than in AIK-treated cells. From our results we propose that after the apoptosis induction the amount of intranuclear calcium decreased dramatically due to the increase of calcium permeability of the nuclear calcium store vesicles. Therefore, increase of the calcium permeability may result from IP(3) receptors translocation to nuclei that can boost the calcium transport through IP(3) receptors.
authors.affiliation: Institute of Molecular Physiology and Genetics, Centre of Excellence for Cardiovascular Research, Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors.forename: Karol
authors.initials: K
authors.lastname: Ondrias
authors.forename: Lubomira
authors.initials: L
authors.lastname: Lencesova
authors.forename: Marta
authors.initials: M
authors.lastname: Sirova
authors.forename: Martina
authors.initials: M
authors.lastname: Labudova
authors.forename: Silvia
authors.initials: S
authors.lastname: Pastorekova
authors.forename: Juraj
authors.initials: J
authors.lastname: Kopacek
authors.forename: Olga
authors.initials: O
authors.lastname: Krizanova
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002166:Camptothecin / Q000494:pharmacology; D053148:Caspase 3 / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells; D010539:Permeability; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: C494828:Bax protein, rat; D001896:Boron Compounds; D053496:Inositol 1,4,5-Trisphosphate Receptors; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D003609:Dactinomycin; D005047:Etoposide; D003907:Dexamethasone; D003513:Cycloheximide; C109986:2-aminoethoxydiphenyl borate; C505410:Casp3 protein, rat; D053148:Caspase 3; D002118:Calcium; D002166:Camptothecin