Name: THIAGO NUNES DE MENEZES
Publication date: 19/05/2017
Advisor:
Name |
Role |
|---|---|
| SILVANA DOS SANTOS MEYRELLES | Co-advisor * |
| SUELY GOMES DE FIGUEIREDO | Advisor * |
Examining board:
| Name |
Role |
|---|---|
| ELISARDO CORRAL VASQUEZ | Internal Examiner * |
| NAZARE SOUZA BISSOLI | Internal Examiner * |
| SILVANA DOS SANTOS MEYRELLES | Co advisor * |
| SUELY GOMES DE FIGUEIREDO | Advisor * |
Summary: The role of plasmatic lipids in the chronic disease may be associated with oxidative stress, which is characterized by redox imbalance. Proteins are molecules involved in almost all biological phenomena and the understanding of the protein regulation may be a source of new therapeutic strategies. Thus, the aim of the present work was analyse
the mitochondrial protein expression in 18-weeks old sildenafil-treated apoE-/- mice as compared to non-treated animals. Previously, the apoE-/- mice presented a plasma lipid profile characteristic of dyslipidemia, and the triacylglycerol, total cholesterol, LDL and
VLDL levels were 5, 14, 6 and 36 times higher than observed from control group (C57), which was not reverted by treatment with sildenafil. Flow cytometry showed in liver cells increased levels of intracellular reactive oxygen species of superoxide anion (~82%),
hydrogen peroxide (~60%), peroxinitrite (~53%) as well as increased apoptotic cells (from ~2% to ~19%). The treatment was able to prevent the production of analysed ROS and reduced the apoptotic cells, restoring the pattern observed in C57 group. It suggests that sildenafil presents an antioxidant action. Differential two-dimensional
electrophoresis coupled with mass spectrometry was applied to study the changes in mitochondrial protein profile in both conditions. The treatment up-regulated urate oxidase (~93%), which degrades the uric acid and it may be consider an antioxidant way. The results also showed that the dyslipidemia induces transferrin up-regutation (~914%), an iron-transport protein. The increase of iron supply may leads to hydrogen peroxide formation by Fenton reaction, contributing to oxidative stress. The animals treated with sildenafil presented this protein down-regulated (~70%) compared with those non-treated, suggesting a redox homeostasis state after treatment with sildenafil.
Our results clearly point to the strong role of sildenafil in mitochondrial ROS production. Up-regulation of urate oxidase and down-regulation of transferrin may represent an important mechanisms of beneficial action of sildenafil in mitochondrial redox imbalance during dyslipidemia.
