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Spg7  -  spastic paraplegia 7 homolog (human)

Mus musculus

Synonyms: AI452278, AU015315, Cmar, PGN, Paraplegin, ...
 
 
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Disease relevance of Spg7

 

High impact information on Spg7

 

Chemical compound and disease context of Spg7

 

Biological context of Spg7

  • PGN also induced phosphorylation and activation of Elk-1, a member of the Ets family of transcription factors [8].
  • One dominant binding site (70 kDa 6.5 pI protein) for bacterial cell wall peptidoglycan (PGN), a macrophage activator and polyclonal B cell mitogen, was demonstrated on mouse B and T lymphocytes and macrophages by photoaffinity cross-linking and two-dimensional polyacrylamide gel electrophoresis [9].
  • The binding was specific for polymeric PGN and was competitively inhibited by unlabeled PGN with IC50 = 48 micrograms/ml (0.38 microM) [9].
  • TLR2(-)/- mice lacked maturation upon stimulation with PGN, as assessed by expression of major histocompatibility complex class II, CD86, cytokine, and chemokine production, fluorescein isothiocyanate-dextran uptake, and mixed lymphocyte reactions, while being completely responsive to LPS [10].
  • OBJECTIVE: These investigations compared peptidoglycan (PGN; TLR2)-induced and immunostimulatory sequence DNA oligodeoxynucleotide (ISS-ODN; TLR9)-induced innate responses and determined how airway exposures to these TLR ligands affect adaptive immunity and the asthmatic phenotype [11].
 

Anatomical context of Spg7

  • Here, we analyze the assembly of paraplegin into m-AAA complexes and monitor consequences of paraplegin deficiency in HSP fibroblasts and in a mouse model for HSP [12].
  • Bacteria and their ubiquitous cell wall component peptidoglycan (PGN) activate the innate immune system of the host and induce the release of inflammatory molecules [8].
  • This study was done to identify some of the transcription factors that regulate the expression of the tnf-alpha gene in macrophages stimulated with PGN [8].
  • We used neutrophils from transgenic SHIP(-/-) and SHIP(+/+) mice that were stimulated with peptidoglycan (PGN) to examine the role of SHIP in TLR2-induced neutrophil activation [13].
  • Finally, we challenged mice with live S. aureus and found a similar degree of TLR2 involvement in leukocyte recruitment to that observed with PGN [2].
 

Associations of Spg7 with chemical compounds

  • PGN, LPS, flagellin, and ISS-ODN induced liver inflammatory infiltrate in EtOH-fed mice but not control mice [14].
  • The PGN-induced increase in Ras activity was inhibited by manumycin A [15].
  • In contrast to the ReLPS-induced effects, the PGN- and sPGN-induced effects were not inhibited by polymyxin B [16].
  • The PGN-induced increase in kappaB luciferase activity was inhibited by NS398, AH6809, AH23848, KT5720, a protein kinase C inhibitor (Ro31-8220), and a p38 MAPK inhibitor (SB203580) [17].
  • The inhibitory effect of DMA7-beta-CyD on NO production was also observed in macrophages stimulated with lipoteichoic acid (LTA), but not peptidoglycan (PGN), polyinosinic-polycytidylic acid (poly I:C) or CpG oligonucleotide (CpG-ODN) [18].
 

Analytical, diagnostic and therapeutic context of Spg7

References

  1. Hereditary spastic paraplegia: respiratory choke or unactivated substrate? Claypool, S.M., Koehler, C.M. Cell (2005) [Pubmed]
  2. The Role of TLR2 In Vivo following Challenge with Staphylococcus aureus and Prototypic Ligands. Mullaly, S.C., Kubes, P. J. Immunol. (2006) [Pubmed]
  3. Mast cells have a pivotal role in TNF-independent lymph node hypertrophy and the mobilization of Langerhans cells in response to bacterial peptidoglycan. Jawdat, D.M., Rowden, G., Marshall, J.S. J. Immunol. (2006) [Pubmed]
  4. Axonal degeneration in paraplegin-deficient mice is associated with abnormal mitochondria and impairment of axonal transport. Ferreirinha, F., Quattrini, A., Pirozzi, M., Valsecchi, V., Dina, G., Broccoli, V., Auricchio, A., Piemonte, F., Tozzi, G., Gaeta, L., Casari, G., Ballabio, A., Rugarli, E.I. J. Clin. Invest. (2004) [Pubmed]
  5. Differential responses of mast cell Toll-like receptors 2 and 4 in allergy and innate immunity. Supajatura, V., Ushio, H., Nakao, A., Akira, S., Okumura, K., Ra, C., Ogawa, H. J. Clin. Invest. (2002) [Pubmed]
  6. SecA2-dependent secretion of autolytic enzymes promotes Listeria monocytogenes pathogenesis. Lenz, L.L., Mohammadi, S., Geissler, A., Portnoy, D.A. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  7. Effect of ashwagandha on lipid peroxidation in stress-induced animals. Dhuley, J.N. Journal of ethnopharmacology. (1998) [Pubmed]
  8. Bacterial peptidoglycan-induced tnf-alpha transcription is mediated through the transcription factors Egr-1, Elk-1, and NF-kappaB. Xu, Z., Dziarski, R., Wang, Q., Swartz, K., Sakamoto, K.M., Gupta, D. J. Immunol. (2001) [Pubmed]
  9. Demonstration of peptidoglycan-binding sites on lymphocytes and macrophages by photoaffinity cross-linking. Dziarski, R. J. Biol. Chem. (1991) [Pubmed]
  10. The role of toll-like receptors (TLRs) in bacteria-induced maturation of murine dendritic cells (DCS). Peptidoglycan and lipoteichoic acid are inducers of DC maturation and require TLR2. Michelsen, K.S., Aicher, A., Mohaupt, M., Hartung, T., Dimmeler, S., Kirschning, C.J., Schumann, R.R. J. Biol. Chem. (2001) [Pubmed]
  11. Airway peptidoglycan and immunostimulatory DNA exposures have divergent effects on the development of airway allergen hypersensitivities. Chisholm, D., Libet, L., Hayashi, T., Horner, A.A. J. Allergy Clin. Immunol. (2004) [Pubmed]
  12. Variable and Tissue-Specific Subunit Composition of Mitochondrial m-AAA Protease Complexes Linked to Hereditary Spastic Paraplegia. Koppen, M., Metodiev, M.D., Casari, G., Rugarli, E.I., Langer, T. Mol. Cell. Biol. (2007) [Pubmed]
  13. Involvement of SHIP in TLR2-induced neutrophil activation and acute lung injury. Strassheim, D., Kim, J.Y., Park, J.S., Mitra, S., Abraham, E. J. Immunol. (2005) [Pubmed]
  14. Differential liver sensitization to toll-like receptor pathways in mice with alcoholic fatty liver. Gustot, T., Lemmers, A., Moreno, C., Nagy, N., Quertinmont, E., Nicaise, C., Franchimont, D., Louis, H., Devière, J., Le Moine, O. Hepatology (2006) [Pubmed]
  15. Peptidoglycan induces nuclear factor-kappaB activation and cyclooxygenase-2 expression via Ras, Raf-1, and ERK in RAW 264.7 macrophages. Chen, B.C., Chang, Y.S., Kang, J.C., Hsu, M.J., Sheu, J.R., Chen, T.L., Teng, C.M., Lin, C.H. J. Biol. Chem. (2004) [Pubmed]
  16. Peptidoglycan induces transcription and secretion of TNF-alpha and activation of lyn, extracellular signal-regulated kinase, and rsk signal transduction proteins in mouse macrophages. Gupta, D., Jin, Y.P., Dziarski, R. J. Immunol. (1995) [Pubmed]
  17. Peptidoglycan-induced IL-6 production in RAW 264.7 macrophages is mediated by cyclooxygenase-2, PGE2/PGE4 receptors, protein kinase A, I kappa B kinase, and NF-kappa B. Chen, B.C., Liao, C.C., Hsu, M.J., Liao, Y.T., Lin, C.C., Sheu, J.R., Lin, C.H. J. Immunol. (2006) [Pubmed]
  18. Inhibitory effects of dimethylacetyl-beta-cyclodextrin on lipopolysaccharide-induced macrophage activation and endotoxin shock in mice. Arima, H., Motoyama, K., Matsukawa, A., Nishimoto, Y., Hirayama, F., Uekama, K. Biochem. Pharmacol. (2005) [Pubmed]
  19. Proinflammatory bacterial peptidoglycan as a cofactor for the development of central nervous system autoimmune disease. Visser, L., Jan de Heer, H., Boven, L.A., van Riel, D., van Meurs, M., Melief, M.J., Zähringer, U., van Strijp, J., Lambrecht, B.N., Nieuwenhuis, E.E., Laman, J.D. J. Immunol. (2005) [Pubmed]
  20. Staphylococcus aureus-derived peptidoglycan induces Cx43 expression and functional gap junction intercellular communication in microglia. Garg, S., Md Syed, M., Kielian, T. J. Neurochem. (2005) [Pubmed]
  21. Toll-like receptor 2 (TLR2) is pivotal for recognition of S. aureus peptidoglycan but not intact bacteria by microglia. Kielian, T., Esen, N., Bearden, E.D. Glia (2005) [Pubmed]
  22. Modification of allergic inflammation in murine model of rhinitis by different bacterial ligands: involvement of mast cells and dendritic cells. Yamamoto, K., Kawamura, I., Ito, J., Mitsuyama, M. Clin. Exp. Allergy (2006) [Pubmed]
 
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