Analysis of metal-regulated metallothionein and heat shock gene expression in HeLa-derived cadmium-resistant cells.
The expression of metallothionein (MT) and heat shock protein gene families was investigated in normal and in HeLa-derived cadmium-resistant cells, named H454. In the absence of amplification of MT genes H454 cells accumulated elevated concentrations of cadmium ions and synthesized higher levels of MT proteins than unselected HeLa cells. Northern blot analyses revealed higher levels of MT mRNAs in the resistant cells than in wild-type cells after Cd2+ and Zn2+ exposure. Evaluation of the cytotoxic potential of the different metals confirmed the high resistance to cadmium of the H454 cells. Two proteins of the heat shock family, hsp70 and GRP78, were synthesized in Cd(2+)-exposed H454 cells at levels comparable to the ones present in Cd(2+)-treated normal cells. Northern blot analyses of the mRNA levels corresponding to these proteins revealed elevated expression of both hsp70 and GRP78 mRNAs in H454 cells upon exposure to cadmium ions and no response to zinc induction. These data suggest the existence in the H454 cells of a cadmium-specific pathway of regulation of MT and heat shock genes.
Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli Federico II, Naples, Italy.
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Cigliano
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Remondelli
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Minichiello
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Mellone
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Martire
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Bonatti
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Leone
D002104:Cadmium / Q000494:pharmacology*; D002352:Carrier Proteins / Q000096:biosynthesis*; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells; D004351:Drug Resistance; D000091342:Endoplasmic Reticulum Chaperone BiP; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D008668:Metallothionein / Q000096:biosynthesis*; D018832:Molecular Chaperones / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects*; D015032:Zinc / Q000494:pharmacology
D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; D002104:Cadmium; D008668:Metallothionein; D015032:Zinc