02307nas a2200361   4500000000100000008004100001260001300042653001200055653001900067653002400086653002300110653001500133653001800148653002700166653001100193653000900204653002500213653002000238653002200258100001400280700001400294700001500308700001500323700001500338700001200353700001700365700001700382245010600399300001100505490000700516520140800523022001401931       2011                            d  c2011 Oct10aAnimals10aAutoantibodies10aAutoimmune Diseases10aBacterial Proteins10aBiomarkers10aChaperonin 6010aDisease Models, Animal10aFemale10aMice10aMycobacterium leprae10aRodent Diseases10aSurvival Analysis1 aParada CA1 aPortaro F1 aMarengo EB1 aKlitzke CF1 aVicente EJ1 aFaria M1 aSant'Anna OA1 aFernandes BL00aAutolytic Mycobacterium leprae Hsp65 fragments may act as biological markers for autoimmune diseases.  a268-760 v513 a<p>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)F(1) mouse hybrids, and their individual anti-rHsp65 IgG2a/IgG1 antibody titer ratio was determined. The results showed orientation toward a T(H)1 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.</p>  a1096-1208