DOI QR코드

DOI QR Code

Studies on the Function of Peroxidasins in Innate Immune System in C. elegans

  • Cho, Jeong Hoon (Department of Biology Education, College of Education, Chosun University)
  • Received : 2019.11.29
  • Accepted : 2019.12.18
  • Published : 2019.12.30

Abstract

Peroxidasin is a unique member of peroxidase family in that it has extracellular matrix (ECM) motif as well as peroxidase activity. Peroxidasins are involved in consolidation the extracellular matrix during development and in innate immune defense. C. elegans has two functional peroxidasins, PXN-1 and PXN-2, and PXN-2 is known to contribute to innate immune system. However, it is not clear of PXN-1 function in innate immune system. Therefore, this study is focused on the function of PXN-1 and the relationship between PXN-1 and PXN-2 in innate defense system in C. elegans. When pxn-1 was knocked down by RNAi, the worm turned to be more resistant to pathogens, Staphylococcus aureus and Pseudomonas aeruginosa and the enhanced resistance was abolished in pxn-1pxn-2 double knock down. By contrast, pxn-2 knock down showed stronger susceptibility to the pathogens. These results suggest that pxn-2 can contribute the pathogen resistance and pxn-1 can suppress the pathogen resistance. To confirm the idea, overexpression experiments were performed. Overexpression of pxn-1 showed more susceptible to pathogens compared to the control and double overexpression of pxn-1pxn-2 overcame the susceptibility of pxn-1 overexpression to the pathogens. On the other hand, pxn-2 overexpression made the worm more resistant to the pathogens and the resistance was maintained in pxn-1pxn-2 double overexpression. The comparison of the susceptibilities to the bacterial pathogens in above mentioned constructs suggests that PXN-1 suppress the function of PXN-2 in defense against bacterial pathogens in Caenorhabditis elegans.

Keywords

References

  1. R. E. Nelson, L. I. Fessler, Y. Takagi, B. Blumberg, D. R. Keene, P. F. Olson, C. G. Parker, and J. H. Fessler, "Peroxidasin: a novel enzyme-matrix protein of Drosophila development", The EMBO journal., Vol. 13, pp. 3438-3447. 1994. https://doi.org/10.1002/j.1460-2075.1994.tb06649.x
  2. J. R. Gotenstein, R. E. Swale, T. Fukuda, C. A. Giurumescu, A. Goncharov, Y. Jin, and A. D. Chisholm, "The C. elegans p eroxidasin P XN-2 i s essential for embryonic morphogenesis and inhibits adult axon regeneration", Development., Vol. 137, pp. 3603-3613. 2010. https://doi.org/10.1242/dev.049189
  3. A. L. Fidler, R. M. Vanacore, S. V. Chetyrkin, V. K. Pedchenko, G. Bhave, V. P. Yin, C. L. Stothers, K. L. Rose, W. H. McDonald, T. A. Clark, D. B. Borza, R. E. Steele, M. T. Ivy, Aspirnauts, J. K. Hudson, and B. G. Hudson, "A unique covalent bond in basement membrane is a primordial innovation for tissue evolution", Proc Natl Acad Sci U S A., Vol. 111, pp. 331-336. 2014. https://doi.org/10.1073/pnas.1318499111
  4. S. J. Klebanoff, "Myeloperoxidase: friend and foe", J Leukoc Biol., Vol. 77, pp. 598-625. 2005 https://doi.org/10.1189/jlb.1204697
  5. G. R. Tiller, and D. A. Garsin, "The SKPO-1 peroxidase functions in the hypodermis to protect Caenorhabditis elegans from bacterial infection", Genetics., Vol. 197, pp. 515-526
  6. R. Shi, Z. Cao, H. Li, J. Graw, G. Zhang, V. J. Thannickal, and G. Cheng G, "Peroxidasin contributes to lung host defense by direct binding and killing of gram-negative bacteria", PLoS pathogens., Vol. 14, e1007026, doi:10.1371/journal.ppat.1007026. 2018.
  7. I. Cho, G. J. Hwang, and J. H. Cho, "pxn-1 and pxn- 2 May Interact Negatively during Neuronal Development and Aging in C. elegans", Molecules and Cells., Vol. 38, pp. 729-733. 2015. https://doi.org/10.14348/molcells.2015.0124
  8. S. Brenner, "The genetics of Caenorhabditis elegans". Genetics., Vol. 77, pp. 71-94. 1974. https://doi.org/10.1093/genetics/77.1.71
  9. R. S. Kamath, M. Martinez-Campos, P. Zipperlen, A. G. Fraser, and J. Ahringer, "Effectiveness of specific RNA-mediated interference through ingested double-stranded RNA in Caenorhabditis elegans", Genome biology., Vol. 2(1): research0002.1- research0002.10, doi:10.1186/gb-2000-2-1-research0002. 2001.
  10. C. Mello, and A. Fire, "DNA transformation", Methods Cell Biol., Vol. 48, pp. 451-482. 1995. https://doi.org/10.1016/S0091-679X(08)61399-0
  11. S. K. Han, D. Lee, H. Lee, D. Kim, H. G. Son, J. S. Yang, S. V. Lee, and S. Kim, "OASIS 2: online application for survival analysis 2 with features for the analysis of maximal lifespan and healthspan in aging research", Oncotarget., Vol. 7, pp. 56147-56152. 2016. https://doi.org/10.18632/oncotarget.11269
  12. Y. Liu, K. G. Kaval, A. van Hoof, and D. A. Garsin, "Heme peroxidase HPX-2 protects Caenorhabditis elegans from pathogens". PLoS Genet., Vol. 15, e1007944, doi:10.1371/journal.pgen.1007944. 2019.