Down-Regulation of the Longevity-Associated Protein SIRT1 in Peripheral Blood Mononuclear Cells of Treated HIV Patients
Por:
Gruevska A, Moragrega ÁB, Galindo MJ, Esplugues JV, Blas-García A and Apostolova N
Publicada:
1 feb 2022
Ahead of Print:
20 ene 2022
Categoría:
Biochemistry, genetics and molecular biology (miscellaneous)
Resumen:
The activity of sirtuin 1 (SIRT1), a class III histone deacetylase with a critical role in several biological functions, decreases with age and its deficiency is associated with many inflammatory and age-related diseases. It also regulates the chronic immune activation and viral latency during an HIV infection. The life-span and particularly the health span of HIV patients are substantially shortened; however, the participation of SIRT1 in these effects is not clear. We performed a prospective cross-sectional monocentric study that included 70 HIV-infected patients and 43 BMI-, age- and sex-matched uninfected individuals. We found that in the PBMCs of the HIV patients, SIRT1 mRNA levels were significantly lower (p < 0.0001). This decrease, which was corroborated at the protein level, occurred irrespectively of the antiretroviral regimen these patients received and was not significantly related to the general, HIV-related or comorbidity-related parameters. The levels of the major mitochondrial sirtuin SIRT3 were not altered. Moreover, the strong correlations of SIRT1 with the leukocyte markers CD8A and CD19 present in the uninfected individuals were absent in the HIV patients. In conclusion, this study showed that the PBMCs of the HIV patients displayed diminished SIRT1 levels and altered correlations of SIRT1 with markers of CD8(+) T cells and B cells, findings which may be relevant for understanding the complex pathogenic milieu in HIV patients.
Filiaciones:
:
Departamento de Farmacología, Universidad de Valencia, 46010 Valencia, Spain
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO), 46020 Valencia, Spain
:
Departamento de Farmacología, Universidad de Valencia, 46010 Valencia, Spain
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO), 46020 Valencia, Spain
Galindo MJ:
Unidad de Enfermedades Infecciosas-Medicina Interna, Hospital Clínico Universitario de Valencia, 46010 Valencia, Spain
:
Departamento de Farmacología, Universidad de Valencia, 46010 Valencia, Spain
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO), 46020 Valencia, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 46010 Valencia, Spain
:
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO), 46020 Valencia, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 46010 Valencia, Spain
Departamento de Fisiología, Universidad de Valencia, 46010 Valencia, Spain
:
Departamento de Farmacología, Universidad de Valencia, 46010 Valencia, Spain
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO), 46020 Valencia, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 46010 Valencia, Spain
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