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Lead interaction with human protamine (HP2) as a mechanism of male reproductive toxicity

  1. Author:
    Quintanilla-Vega, B.
    Hoover, D. J.
    Bal, W.
    Silbergeld, E. K.
    Waalkes, M. P.
    Anderson, L. D.
  2. Author Address

    Quintanilla-Vega B IPN, CINVESTAV, Secc Toxicol Ambiental Ave IPN 2508 Mexico City 07360 DF Mexico IPN, CINVESTAV, Secc Toxicol Ambiental Mexico City 07360 DF Mexico NIEHS, NCI Res Triangle Pk, NC 27709 USA Univ Maryland, Sch Med, Program Human Hlth & Environm Baltimore, MD 21201 USA Univ Maryland, Sch Med, Dept Anat & Neurobiol Baltimore, MD 21201 USA Univ Wroclaw, Fac Chem PL-50138 Wroclaw Poland NCI, Comparat Carcinogenesis Lab, FCRDC Frederick, MD 21702 USA
    1. Year: 2000
  1. Journal: Chemical Research in Toxicology
    1. 13
    2. 7
    3. Pages: 594-600
  2. Type of Article: Article
  1. Abstract:

    During spermatogenesis, histones are replaced by protamines, which condense and protect sperm DNA. In humans, zinc contributes to sperm chromatin stability and binds to protamine P2 (HP2). Chemical interactions with nuclear protamines, which prevent normal sperm chromatin condensation, may induce changes in the sperm genome and thus affect fertility and offspring development. Since lead has a high affinity for zinc-containing proteins, we investigated lead interactions with HP2 as a novel mechanism of its toxicity to sperm. UV/vis and CD spectroscopy results indicated that HP2 binds Pb2+ at two different sites, causing a conformational change in the protein. They also provided evidence that thiol groups are primarily involved in Zn2+ and Pb2+ binding to HP2 and that HP2 may have additional binding sites for Pb2+ not related to Zn2+. HP2 affinities for Pb2+ and Zn2+ were very similar, suggesting that Pb2+ can compete with or replace Zn2+ in HP2 in vivo. This interaction of lead with HP2 resulted in a dose-dependent decrease in the extent of HPS-DNA binding, although lead interaction with DNA also contributed to this effect. Therefore, the ability of lead to decrease the level of HP2-DNA interaction may result in alterations to sperm chromatin condensation, and thus in reduced fertility. [References: 54]

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