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SPLICE VARIANT SPECIFIC UPREGULATIONOF CA+2/CALMODULIN DEPENDENT PROTEIN KINASE 1G BY PYRETHROID INSECTICIDES IN VIVO.
Citation:
HARRILL, J. AND K. M. CROFTON. SPLICE VARIANT SPECIFIC UPREGULATIONOF CA+2/CALMODULIN DEPENDENT PROTEIN KINASE 1G BY PYRETHROID INSECTICIDES IN VIVO. Presented at International Neurotoxicology , San Antonio, TX, November 11 - 14, 2007.
Impact/Purpose:
The present study tests the hypothesis that changes in Camk1g expression following acute pyrethroid exposure are due to a specific increase in the Camk1g1 (Ca+2-sensitive) splice variant and not the Ca+2-insensitive splice variant Camk1g2.
Description:
Pyrethroid insecticides induce neurotoxicity in mammals by interfering with ion channel function in excitable neuronal membranes. Previous work demonstrated dose-dependent increases in expression of Ca+2/calmodulin dependent protein kinase (Camk1g) mRNA following acute deltamethrin (DLT) and permethrin (PERM) exposure. The present study tests the hypothesis that changes in Camk1g expression following acute pyrethroid exposure are due to a specific increase in the Camk1g1 (Ca+2-sensitive) splice variant and not the Ca+2-insensitive splice variant Camk1g2. Long-Evans rats (n = 8 / group) were acutely exposed (p.o) with: PERM (1, 10, 40, 100 mg/kg), DLT (0.3, 1, 3 mg/kg) or corn oil vehicle. Cerebrocortical tissue was collected at 6 h post-dosing. In addition, rats were exposed to PERM (100 mg/kg) or DLT (3 mg/kg) and cerebrocortical tissue collected at 1, 3, 6 or 9 hours with time matched vehicle controls. Expression of Camk1g1 and Camk1g2 mRNA was measured via quantitative RT-PCR and quantified with the 2-CT method. Dose-dependent increases in Camk1g1 mRNA expression were observed for DLT and PERM at 6 h. In addition, a dose-dependent increase in Camk1g2 was also observed at 6 h with DLT only, although it was very small in magnitude (<1.2-fold). The increases in Camk1g1 expression for DLT and PERM peak between 3 & 6 h post-exposure and return to control levels by 9 h. Correlation analysis demonstrated that dose- and time- dependent increases in Camk1g mRNA expression are due primarily to increases in the Camk1g1 splice variant. Future work includes quantification of Camk1g1 protein expression following pyrethroid exposure as this protein is a mediator of activity-dependent neuronal morphogenesis, a process that may be disrupted by pyrethroid exposure.