The biochemical and molecular biological mechanisms responsible for cerebral micro-vasculopathy following acute lead toxicity remain poorly-defined. Increasing evidence points to a role for protein kinase C (PKC), an enzyme that regulates many cellular processes such as growth and differentiation. The proposed experiments were designed to test the hypothesis that lead activation of PKC interferes with the cascade of PKC-mediated processes that regulated protein phosphorylation, gene expression, and microvascular cell behavior. The goals of the current proposal are to determine the mechanism by which lead increased expression of c-fos in the vitro and in the vivo. In the aim 1 the investigators will determine if lead increases mRNA levels of immediate early response genes(IERGs) by enhancing gene transcription or slowing mRNA degradation. If transcriptional events are implicated than lead-sensitive c-fos transcriptional regulatory elements will be determined.
Aim 2 will determine if lead induced increases in the IERG proteins and AP-1 activity can regulate the expression of other important genes.
Aim 3 was designed to determine if lead alters IERG expression in the vivo. The fundamental goal of the experiments is to define the biochemical and molecular mechanisms essential to a more complete understanding of lead toxicity within the central nervous system.
| Cheong, Jae Hoon; Bannon, Desmond; Olivi, Luisa et al. (2004) Different mechanisms mediate uptake of lead in a rat astroglial cell line. Toxicol Sci 77:334-40 |
| Hossain, Mir Ahamed; Russell, Juliet C; Miknyoczki, Sheila et al. (2004) Vascular endothelial growth factor mediates vasogenic edema in acute lead encephalopathy. Ann Neurol 55:660-7 |
| Patra, Ramesh C; Blue, Mary E; Johnston, Michael V et al. (2004) Activity-dependent expression of Egr1 mRNA in somatosensory cortex of developing rats. J Neurosci Res 78:235-44 |
| Johnston, Michael V (2004) Clinical disorders of brain plasticity. Brain Dev 26:73-80 |
| Johnston, Michael V (2003) Injury and plasticity in the developing brain. Exp Neurol 184 Suppl 1:S37-41 |
| Bannon, Desmond I; Abounader, Roger; Lees, Peter S J et al. (2003) Effect of DMT1 knockdown on iron, cadmium, and lead uptake in Caco-2 cells. Am J Physiol Cell Physiol 284:C44-50 |
| Glenn, Barbara S; Stewart, Walter F; Links, Jonathan M et al. (2003) The longitudinal association of lead with blood pressure. Epidemiology 14:30-6 |
| Olivi, Luisa; Sisk, Jeanne; Bressler, Joseph (2003) The involvement of lipid activators of protein kinase C in the induction of ZIF268 in PC12 cells exposed to lead. Neurochem Res 28:65-71 |
| Donovan, Stacy L; Mamounas, Laura A; Andrews, Anne M et al. (2002) GAP-43 is critical for normal development of the serotonergic innervation in forebrain. J Neurosci 22:3543-52 |
| Kim, Kyung-Ah; Chakraborti, Tamal; Goldstein, Gary et al. (2002) Exposure to lead elevates induction of zif268 and Arc mRNA in rats after electroconvulsive shock: the involvement of protein kinase C. J Neurosci Res 69:268-77 |
Showing the most recent 10 out of 21 publications
