文摘
We have demonstrated previously that Ni(II) binds to the C-terminal -TESHHKAKGK motifof isolated bovine histone H2A. At physiological pH, the bound Ni(II) assists in hydrolysis ofthe E-S peptide bond in this motif that results in a cleavage of the terminal octapeptideSHHKAKGK off the histone's C-tail. To test if the hydrolysis could also occur in living cells,we cultured CHO (Chinese hamster ovary), NRK-52 (rat renal tubular epithelium), and HPL1D(human lung epithelium) cells with 0.1-1 mM Ni(II) for 3-7 days. As found by gelelectrophoresis, Western blotting, and liquid chromatography/mass spectrometry, histonesextracted from the cells contained a new fraction of histone H2A lacking the terminaloctapeptide (q-H2A). The abundance of q-H2A increased with Ni(II) concentration and exposuretime. It can be anticipated that the truncation of histone H2A may alter chromatin structureand affect gene expression. The present results provide evidence for novel mechanisms ofepigenetic effects of Ni(II) that may be involved in nickel toxicity and carcinogenesis.
