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Expression of Calponin 3 in the Striatum Following 3-Nitropropionic Acid-induced Neurotoxicity

선조체에서 3-nitropropionic acid 투여 후 calponin 3의 발현 연구

  • Choi, Yun-Sik (Department of Pharmaceutical Science and Technology, Catholic University of Daegu)
  • 최윤식 (대구가톨릭대학교 제약산업공학과)
  • Received : 2012.12.11
  • Accepted : 2012.12.28
  • Published : 2013.01.30

Abstract

Calponin 3 is an F-actin-binding protein and plays a key role in regulating spine plasticity and synaptic activity in neurons. Unlike the other subtypes, calponin 1 and 2, which are expressed in smooth and cardiac muscle cells, calponin 3 is highly expressed in the brain. The goal of this study was to elucidate the spatiotemporal expression pattern of calponin 3 following repeated administration of 3-nitropropionic acid in mice. The repeated administration of 3-nitropropionic acid generated necrotic neuronal cell death in the striatum. Calponin 3 was up-regulated in the neuroprotective penimbral region from 1.5 days after the last injection and thereafter. Double immunofluorescence study revealed that calponin 3 was induced in GFAP-positive astrocytes. These results suggest that calponin 3 induction in the neuroprotective penumbral area following 3-nitropropionic acid intoxication may play a key role in reactive astrogliosis in the striatum.

Calponin 3는 F-actin과 결합하는 단백질로 신경계의 가소성과 시냅스 활성을 조절하는데 중요한 역할을 하는 것으로 알려져 있다. 평활근과 심장근에 발현되는 calponin 1과 calponin 2와는 다르게 calponin 3는 뇌 조직에 많이 발현되어 있는 것으로 보고되고 있다. 본 연구는 마우스에서 3-nitropropionic acid를 투여하여 선조체에 비가역적 신경 손상을 주었을 때 calponin 3의 발현 양상을 알아보기 위하여 진행되었다. 본 연구 결과 3-nitropropionic acid를 마우스에 투여하였을 때 선조체에서 신경조직의 괴사가 일어남을 관찰하였으며 calponin 3는 약물 투여 후 1.5일부터 서서히 발현되는 것을 확인하였다. 특히, calponin 3는 신경조직의 괴사가 일어나는 부위의 주변부에서 발현되는 것을 확인하였으며 형광 이중면역 염색법으로 확인한 결과 GFAP를 발현하는 별아교세포에서 발현됨을 최초로 밝혔다. 따라서, calponin 3가 3-nitropropionic acid의 독성에 저항성을 나타내는 부위에서 별아교세포에서만 특이적으로 발현되는 것으로 보아 calponin 3는 별아교세포에 의한 신경아교증에 중요한 역할을 하는 것으로 추측된다.

Keywords

References

  1. Beal, M. F., Brouillet, E., Jenkins, B., Henshaw, R., Rosen, B. and Hyman, B. T. 1993. Age-dependent striatal excitotoxic lesions produced by the endogenous mitochondrial inhibitor malonate. J Neurochem 61, 1147-1150. https://doi.org/10.1111/j.1471-4159.1993.tb03633.x
  2. Brouillet, E., Jenkins, B. G., Hyman, B. T., Ferrante, R. J., Kowall, N. W., Srivastava, R., Roy, D. S., Rosen, B. R. and Beal, M. F. 1993. Age-dependent vulnerability of the striatum to the mitochondrial toxin 3-nitropropionic acid. J Neurochem 60, 356-359. https://doi.org/10.1111/j.1471-4159.1993.tb05859.x
  3. Calkins, M. J., Vargas, M. R., Johnson, D. A. and Johnson, J. A. 2010. Astrocyte-specific overexpression of Nrf2 protects striatal neurons from mitochondrial complex II inhibition. Toxicol Sci 115, 557-568. https://doi.org/10.1093/toxsci/kfq072
  4. Choi, Y. S., Lee, B., Cho, H. Y., Reyes, I. B., Pu, X. A., Saido, T. C., Hoyt, K. R. and Obrietan, K. 2009. CREB is a key regulator of striatal vulnerability in chemical and genetic models of Huntington's disease. Neurobiol Dis 36, 259-268. https://doi.org/10.1016/j.nbd.2009.07.014
  5. Ferhat, L., Esclapez, M., Represa, A., Fattoum, A., Shirao, T. and Ben-Ari, Y. 2003. Increased levels of acidic calponin during dendritic spine plasticity after pilocarpine-induced seizures. Hippocampus 13, 845-858. https://doi.org/10.1002/hipo.10136
  6. Haag, J. and Aigner, T. 2007. Identification of calponin 3 as a novel Smad-binding modulator of BMP signaling expressed in cartilage. Exp Cell Res 313, 3386-3394. https://doi.org/10.1016/j.yexcr.2007.08.003
  7. Han, Y., Yin, H., Xu, Y., Zhu, Q., Luo, J., Wang, X. and Chen, G. 2012. Increased expression of calponin-3 in epileptic patients and experimental rats. Exp Neurol 233, 430-437. https://doi.org/10.1016/j.expneurol.2011.11.014
  8. Huang, Q. Y., Wei, C., Yu, L., Coelho, J. E., Shen, H. Y., Kalda, A., Linden, J. and Chen, J. F. 2006. Adenosine A2A receptors in bone marrow-derived cells but not in forebrain neurons are important contributors to 3-nitropropionic acid-induced striatal damage as revealed by cell-type-selective inactivation. J Neurosci 26, 11371-11378. https://doi.org/10.1523/JNEUROSCI.1907-06.2006
  9. Kake, T., Kimura, S., Takahashi, K. and Maruyama, K. 1995. Calponin induces actin polymerization at low ionic strength and inhibits depolymerization of actin filaments. Biochem J 312, 587-592.
  10. Kumar, P., Kalonia, H. and Kumar, A. 2011. Role of LOX/COX pathways in 3-nitropropionic acid-induced Huntington's disease-like symptoms in rats: protective effect of licofelone. Br J Pharmacol 164, 644-54. https://doi.org/10.1111/j.1476-5381.2011.01418.x
  11. Plantier, M., Fattoum, A., Menn, B., Ben-Ari, Y., Der Terrossian, E. and Represa, A. 1999. Acidic calponin immunoreactivity in postnatal rat brain and cultures: subcellular localization in growth cones, under the plasma membrane and along actin and glial filaments. Eur J Neurosci 11, 2801-2812. https://doi.org/10.1046/j.1460-9568.1999.00702.x
  12. Rami, G., Caillard, O., Medina, I., Pellegrino, C., Fattoum, A., Ben-Ari, Y. and Ferhat, L. 2006. Change in the shape and density of dendritic spines caused by overexpression of acidic calponin in cultured hippocampal neurons. Hippocampus 16, 183-197. https://doi.org/10.1002/hipo.20145
  13. Takahashi, K., Hiwada, K. and Kokubu, T. 1986. Isolation and characterization of a 34,000-dalton calmodulin- and F-actin-binding protein from chicken gizzard smooth muscle. Biochem Biophys Res Commun 141, 20-26. https://doi.org/10.1016/S0006-291X(86)80328-X
  14. Takahashi, K., Hiwada, K. and Kokubu, T. 1988. Vascular smooth muscle calponin. A novel troponin T-like protein. Hypertension 11, 620-626. https://doi.org/10.1161/01.HYP.11.6.620
  15. Takahashi, K. and Nadal-Ginard, B. 1991. Molecular cloning and sequence analysis of smooth muscle calponin. J Biol Chem 266, 13284-13288.
  16. Tomé, M., Siladzic, E., Santos-Silva, A. and Barnett, S. C. 2007. Calponin is expressed by subpopulations of connective tissue cells but not olfactory ensheathing cells in the neonatal olfactory mucosa. BMC Neurosci 18, 74.
  17. Wu, K. C. and Jin, J. P. 2008. Calponin in non-muscle cells. Cell Biochem Biophys 52, 139-148. https://doi.org/10.1007/s12013-008-9031-6