Banca de QUALIFICAÇÃO: AQUILES SALES CRAVEIRO SARMENTO

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
DISCENTE : AQUILES SALES CRAVEIRO SARMENTO
DATA : 01/03/2019
HORA: 09:00
LOCAL: Sala SS1 - Departamento de Biologia Celular e Genética
TÍTULO:

Oxidative and Endoplasmic Reticulum Stresses are Associated with Generalized Congenital Lipodystrophy Type 2.

PALAVRAS-CHAVES:

Seipin; BSCL2; Adiponectin; Oxidative stress; Endoplasmic Reticulum Stress

PÁGINAS: 107
GRANDE ÁREA: Ciências Biológicas
ÁREA: Bioquímica
RESUMO:

Congenital Generalized Lipodystrophy Type 2 is caused by mutations in BSCL2 gene, which encodes to the seipin protein. Characterized by the almost complete lack of adipose tissue from birth, this syndrome has some characteristics in common with obesity, such as hypertriglyceridemia, hyperglycemia, increased LDL-c, decreased HDL-c, and hypoadiponectinemia. In obese patients, these laboratory findings cause important intracellular stresses, such as oxidative and endoplasmic reticulum (ER) stress. We hypothesized that these characteristics are also important for the development of these phenomena in people with lipodystrophies, mainly because seipin is an ER protein and its mutations can generate dysfunction in this organelle. Our objective was to quantify markers of these two stresses in total leukocyte and plasma from people living in northeastern Brazil, presenting the mutation rs786205071 (325dupA). The results indicated increased transcription of OGG1, αOGG1,APEX1 and NFE2L2. In addition, the increase of GSSG:GSH ratio was used as a plasma marker of systemic oxidative stress, as well as an increase of, malondialdehyde which reflects events of lipid peroxidation. Positive correlations between leukocyte transcripts of APEX1 and OGG1 with the increase of triglycerides and decrease of HDL-c in plasma indicated that this stress is secondary to these metabolic parameters. These cells also had a greater amount of oxidized DNA lesions, which correlated with OGG1 and NFE2L2 transcription. We also observed that the expression of that last gene proportionally increased according to the adiponectin concentrations in the blood, showing that this hormone has a role in orchestrating the antioxidant response even in diminished amounts. Regarding to ER stress, we also found increased XBP1 splicing and decreased DDIT3 transcription, findings related to mild dysfunctions in this organelle. In addition, the HSPA5 and P4HB chaperone concentrations were not increased in our cellular model. These two stresses also did not culminate in the increased cleavage of procaspase-3, helping to maintain the appropriated number of leukocytes in the blood. Although BSCL2 gene showed a decreased transcription pattern in this population, our data suggest that its transcript may have a slight influence on ER stress, since the mutation in question removes important amyloidogenic sequences that predispose to this phenomenon. Together, our results demonstrate that oxidative stress and ER are mainly related to the increase of TG, decrease of HDL-c and adiponectin, with an indirect influence of seipin loss of function in type 2 lipodystrophy.

MEMBROS DA BANCA:
Externo ao Programa - 2087759 - ANDRE DUCATI LUCHESSI
Presidente - 1880243 - DANIEL CARLOS FERREIRA LANZA
Interno - 1513597 - JOAO PAULO MATOS SANTOS LIMA