Autolytic Mycobacterium leprae Hsp65 fragments may act as biological markers for autoimmune diseases

详细信息    查看全文

• 作者：Carolina Angé ; lica Parada^a ; ^c ; ¹ ; Fernanda Portaro^b ; ¹ ; ^{fcvportaro@butantan.gov.br"" rel=""nofollow} ; Eliana Blini Marengo^b ; Clé ; cio Fernando Klitzke^a ; Elisabete José ; Vicente^c ; Marcella Faria^a ; Osvaldo Augusto Sant&#x2019 ; Anna^b ; Beatriz Lieblich Fernandes^a
• 关键词：Autolysis ; Mycobacterium leprae Hsp65 ; Peptides ; Systemic lupus erythematosus ; Anti-Hsp65 antibodies ; (NZBxNZW) F₁ mouse
• 刊名：Microbial Pathogenesis
• 出版年：2011
• 出版时间：October 2011
• 年：2011
• 卷：51
• 期：4
• 页码：268-276
• 全文大小：552 K

文摘

Investigating the proteolytic activity of the recombinant Mycobacterium leprae Heat Shock Protein of 65 kDa (rHsp65), chaperonin 2 (cpn2), we observed that it displays high instability. The fragmentation process starts at the C-terminus followed by progressive degradation of the N-terminus, which leads to a stable fragment comprising the middle region of the molecule. Urea was able to prevent autolysis, probably due to its denaturing action, while EDTA increased degradation levels indicating the need for metal ions. Peptides originated from autolysis were purified and analyzed by mass spectrometry, generating a continuous map. Since the bacteria and mammalian Hsp60 are known to be targets of the immune response and have been implicated in autoimmune diseases and chronic inflammation, the in vivo effect of rHsp65 peptides was evaluated in the spontaneous Systemic Lupus Erythematosus (SLE) model developed by the (NZB/NZW)F₁ mouse hybrids, and their individual anti-rHsp65 IgG2a/IgG1 antibody titer ratio was determined. The results showed orientation toward a T_H1 responsiveness, and the treatment with the rHsp65 peptides diminished the environmental variance of the survival time of treated animals. These results outline the fact that environmental factors may also act through the modified stability expression of Heat Shock Proteins intervening during autoimmune processes.