Protein kinase C activity and the relations between blood lead and neurobehavioral function in lead workers

Kyu Yoon Hwang, Byung Kook Lee, Joseph P. Bressler, Karen I. Bolla, Walter F. Stewart, Brian S. Schwartz

Research output: Contribution to journalArticle

Abstract

At picomolar concentrations, lead activates protein kinase C (PKC). This activation has been implicated in the neurotoxicity of lead. No prior study has evaluated the association of PKC activity with neurobehavioral function in humans. The purpose of this study was to determine whether PKC activity is associated with neurobehavioral function or modifies the relationship between blood lead levels and neurobehavioral test scores. In this cross-sectional study of 212 current lead workers in the Republic of Korea, we assessed blood lead levels, neurobehavioral test scores, and PKC activity. PKC activity was determined by measuring the levels of phosphorylation of three erythrocyte membrane proteins (spectrin and the 52-kDa and 48-kDa subunits of band 4.9), using an in vitro back-phosphorylation assay. When linear regression was used to control for confounding variables, blood lead was a significant predictor of decrements in performance on tests of psychomotor function, manual dexterity, and executive ability. In linear regression models, back-phosphorylation levels were not associated with neurobehavioral test scores, but when dichotomized at the median, back-phosphorylation levels modified the relationship between blood lead and test scores. For spectrin and the 52-kDa subunits of band 4.9,5,2, and 5 of 14 interaction terms, respectively, has associated p-values < 0.10, all with positive signs, indicating that blood lead was associated with worse test scores only in subjects with lower back-phosphorylation levels. These data indicate that blood lead levels are associated with decrements in neurobehavioral test scores, mainly in the domains of manual dexterity and psychomotor function, but only in subjects with lower in vitro back-phosphorylation levels, which is equivalent to higher in vivo PKC activity. We hypothesize that subjects with higher PKC activity in the presence of lead may be more susceptible to the health effects of lead.

Original languageEnglish (US)
Pages (from-to)133-138
Number of pages6
JournalEnvironmental health perspectives
Volume110
Issue number2
DOIs
StatePublished - Jan 1 2002

    Fingerprint

Keywords

  • Back-phosphorylation
  • Blood lead
  • Neurobehavioral function
  • Protein kinase C
  • Susceptibility

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

Cite this