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| Author(s): |
José Antonio Tavares de Albuquerque
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2011-09-13 |
| Examining board members: |
Lourdes Isaac;
Luciana Amaral Haddad;
Nancy Starobinas;
Denise Vilarinho Tambourgi;
Dewton de Moraes Vasconcelos
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| Advisor: | Lourdes Isaac |
| Abstract | |
Factor H (FH) is one of the most important regulatory proteins of the alternative pathway of the complement system (CS). In this study, we investigated the consequences of FH Arg127His mutation to the secretion ratio of this protein by skin fibroblasts in vitro. We stimulated the FH synthesis from patient and normal control with IFN<font face=\"Symbol\">g when we observed that the patient cells were able to synthetize FH, however this mutant protein was mainly retained at the endoplasmic reticulum. In parallel, we transfected Cos-7 cells with plasmids containing CG453T<font face=\"Symbol\">® CA453T mutation and observed that the mutation was responsible for the delay in the FH secretion. Although the mutation reduced the FH secretion, we observed that the FH function was not affected. Thus, we evaluated whether the treatment with chemical chaperones could release FH to the culture supernant. We observed that patients fibroblasts treated increased the secretion of FH. In conclusion, we suggest the use of these chemical chaperones as a potential alternative therapeutic to improve the patients survival. (AU) | |