Metal binding of metallothioneins in human astrocytomas (U87 MG, IPDDC-2A).
Astroglia cells structurally and nutritionally support neurons in the central nervous system. They play an important role in guiding the construction of the nervous system and controlling the chemical and ionic environment of neurons. They also represent the major sites for accumulation and immobilisation of toxic metal ions most probably connected with metallothioneins. For this reason astroglia cells possess high cytosolic levels of metallothioneins I, II and III (MT-I,II,III). Our aim was to establish the inducibility and metal binding of MTs in two human astrocytoma cell lines, U87 MG (astrocytoma-glioblastoma, grade IV) and IPDDC-2A (astrocytoma, grade II), on exposure to cadmium chloride (1 microM). MTs were identified by molecular weight (size exclusion chromatography) and their metal content (Cd, Zn and Cu) to follow the interactions between metals. We showed that MTs are constitutively expressed in both human astrocytoma cell lines. In accordance with the higher malignancy grade of U87 MG, the amount of MTs was higher in U87 MG than in IPDDC-2A cells. After 24 hours of exposure to Cd their expression greatly increased in both cell lines and they were capable of immobilising almost all water soluble Cd. Induction of MTs in U87 MG cells was additionally followed up to 48 hours with exposure to different concentrations of CdCl(2) (1, 10 microM). Induction was a time dependent process throughout the period. Isoform III (identified by chromatographic separation of isoform III from I/II) was present at all exposure times, but only in traces with respect to the prevailing amounts of MT-I/II isoforms. So induction can be attributed to isoform I/II only.
Znidaric
Magda Tusek
MT
National Institute of Biology, Vecna pot 111, 1000, Ljubljana, Slovenia. magda.tusek.znidaric@nib.si
Pucer
Anja
A
Fatur
Tanja
T
Filipic
Metka
M
Scancar
Janez
J
Falnoga
Ingrid
I
D001254:Astrocytoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D019256:Cadmium Chloride / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008668:Metallothionein / Q000378:metabolism*; D008670:Metals / Q000378:metabolism* / Q000633:toxicity; D011485:Protein Binding / Q000502:physiology
D008670:Metals; D008668:Metallothionein; D019256:Cadmium Chloride