Effects of PCB Congeners in Rodent Neuronal Cells in Culture : Effects of Chitosan

PCB 이성질체가 설치류 신경세포에 미치는 영향: 키토산의 효과

  • Kim, Sun-Young (Catholic University of Daegu, School of Medicine, Department of Pharmacology) ;
  • Lee, Hyun-Gyo (Catholic University of Daegu, School of Medicine, Department of Pharmacology)
  • 김선영 (대구가톨릭대학교 의과대학 약리학교실) ;
  • 이현교 (대구가톨릭대학교 의과대학 약리학교실)
  • Published : 2007.09.30

Abstract

The present study attempted to analyze the mechanism of PCB-induced neurotoxicity with respect to the PKC signaling. Since the developing neuron is particularly sensitive to PCB-induced neurotoxicity, we isolated cerebellar granule cells derived from 7-day old SD rats and grew cells in culture for additional 7 days to mimic PND-14 conditions. Only non-coplanar PCBs at a high dose showed a significant increase of total PKC activity at $[^3H]PDBu$ binding assay, indicating that non-coplanar PCBs are more neuroactive than coplanar PCBs in neuronal cells. PKC isoforms were immunoblotted with respective monoclonal antibodies. PKC-alpha and-epsilon were activated with non-coplanar PCB exposure. The result suggests that coplanar PCBs have a PKC pathway different from non-coplanar PCBs. Activation of PKC with exposure was dampened with treatment of high molecular weight of chitosan. Chilean (M.W. > 1,000 kDa) inhibited the total activity of PKC induced by the non-coplanar PCBs. Translocation of PKC isoforms was also inhibited by the high molecular weight of chitosan. The study demonstrated that non-coplanar PCBs are more potent neurotoxic congeners than coplanar PCBs and the alteration of PKC activities by PCB exposure can be blocked with the treatment of chitosan. The results suggest a potential use of chitosan as a means of nutritional intervention to prevent the harmful effects of pollutant-derived diseases.

Keywords

References

  1. Abraham K, Papke O and Wahn H. Changes of Biological parameter in breast-fed infants due to PCDD/PCDF/ PCB background exposure, Organohalogen Comp 1999; 44: 59-61
  2. Eriksson P. Developmental neurotoxicity of environmental agents in the neonates, Neurotoxiclolgy 1997; 18: 719-726
  3. Kitamura K and Morita M. Effect of chlorophyllin-chitosan on excretion of dioxins in a healthy man, Env. Sci. Technol 2005; 39: 1084-1091 https://doi.org/10.1021/es048577u
  4. Kodavanti PRS and Tilson HA. Structure-activity relationship of potentially neurotoxic PCB congeners in the rats, Neurotoxicol 1997; 18: 425-442
  5. Kodavanti PRS, Shin D and Tilson HA. Comparative effects of two PCB congeners on ca homeostasis in rat cerebellar granule cells, Toxicol. Appl. Pharmacol 1993; 123: 97-106 https://doi.org/10.1006/taap.1993.1226
  6. Kodavanti PRS, Ward TR and Tilson HA. Inhibition of microsomal and mitochondrial Ca sequestration in rat cerebellum by PCB mixture, Arch. Toxicol 1996; 70: 150-157 https://doi.org/10.1007/s002040050254
  7. Rahaman SO, Ghosh S and Sarkar PK. Hypothyroidism in the developing brain is associated with marked oxidative stress and aberrant intraneuronal accumulation of neurofilaments, Neurosci Res 2001; 40: 273-279 https://doi.org/10.1016/S0168-0102(01)00237-1
  8. Safe S. PCBs; Environmetal impact, biochemical and toxic responses and implications for risk assessment, Crit. Rev. Toxicol 1994; 24: 87-149 https://doi.org/10.3109/10408449409049308
  9. Tilson HA and Kodavanti PRS. Neurochemical effects of PCBs; an overview and identification of research needs, Neurotoxicol 1997; 18: 727-744
  10. Van den Berg M and Birnbaum L. Toxic equivalency factors for PCB, PCDD, PCDF for humans and wildlife, Env. Health. Persp 1998; 106: 775-792 https://doi.org/10.2307/3434121
  11. Vreugdenhil H, Lanting S and Pantadin S. Prenatal and postnatal PCB and dioxin exposure and cognitive ability in Dutch cohort, Organohalogen Comp 1999; 44: 421-425
  12. Weisgla-Kuperus N. Neurodevelopmental, immunological and endocrinological indices of prenatal human exposure to PCBs and Dioxins, Chemosphere 1998; 37: 9-12
  13. WHO. Levels of PCBs, PCDD, and PCDF in breast milk; Environmental Health Series No.3, WHO regional office, Copenhagen 1996
  14. Yang JH and Kodavanti PRS. Possible molecular targets of halogenated aromatic hydrocarbons in neuronal cells; structure-activity relationship, Biochem, Biophys. Res. Commun 2001; 280: 1372-1377 https://doi.org/10.1006/bbrc.2001.4283
  15. Yang JH, Der-Yellin EC and Kodavanti PRS. Alteration in brain protein kinase C isoforms following developmental exposure to PCB mixture, Molecular Brain Res 2003; 109: 176-190
  16. Yang JH, Kim SY, Lee JH, Lee HG and Kim MY. Possible intracellular targets for TCDD in cerebellar granule cells, Organohalogen compounds 2003; 65: 20-23