The effect of lead on the metabolism of a nuclear matrix protein which becomes prominent in lead-induced intranuclear inclusion bodies.
The influence of lead and calcium on the metabolism of a nuclear matrix protein has been studied in mouse neuroblastoma 2a (Nb2a) cells. This protein, p32/6.3, has an unusual distribution in that it is relatively abundant only in normal neural tissues and in intranuclear inclusion bodies induced in kidney tubule-lining cells of chronically lead-intoxicated animals (Egle, P. M., and Shelton, K. R. (1986) J. Biol. Chem. 261, 2294-2298). The mechanism(s) whereby lead increases p32/6.3 content are of interest, but its slow accumulation in intact animals over a period of weeks to months precludes studies with metabolic inhibitors. However, the enriched levels of p32/6.3 in mouse neuroblastoma 2a (Nb2a) cells permit these studies. The relative abundance of this protein was found to increase in mouse Nb2a cells after 1- and 3-day exposures to lead. This increase could be attributed to a decreased rate of degradation rather than either increased transcription or increased translation. A role for calcium in p32/6.3 regulation was also explored. Although neither increased extracellular calcium nor calcium ionophores had an effect, treatment of the cells with the calcium chelator [ethylenebis(oxyethylenenitrilo)]tetraacetic acid decreased p32/6.3 levels in a concentration-dependent manner, suggesting a role for calcium in the normal metabolism of the protein.
Klann
E
E
Department of Biochemistry and Molecular Biophysics, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Shelton
K R
KR
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002531:Cerebellum / Q000166:cytology; D003513:Cycloheximide / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D002479:Inclusion Bodies / Q000187:drug effects / Q000378:metabolism*; D007854:Lead / Q000494:pharmacology*; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D015530:Nuclear Matrix / Q000187:drug effects / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D051381:Rats; D014407:Tumor Cells, Cultured
D005971:Glutamates; D009687:Nuclear Proteins; D007854:Lead; D018698:Glutamic Acid; D004533:Egtazic Acid; D003513:Cycloheximide; D002118:Calcium