Unraveling the dynamic oxidative processes after ischemia/reperfusion in the heart using new proteomics approaches
Author
Castañs García, CeliaEntity
UAM. Departamento de BioquímicaDate
2019-09-04Subjects
Arterias coronarias - Enfermedades; Reperfusión miocárdica - Tesis; Biología y Biomedicina / BiologíaNote
Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica. Fecha de lectura: 04-06-2019Esta tesis tiene embargado el acceso al texto completo hasta el 04-12-2020
Esta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional.
Abstract
After an episode of coronary artery occlusion, myocardial response to
reperfusion does not remain stable during time. Although there are many
relevant proteomic changes taking place in the tissue, systematic studies are
lacking on the protein modification changes occurring in the post-reperfused
myocardium along the first week after I/R. In this Doctoral Thesis we present the
application of global PTMs analysis combined with the mapping of redox-active
thiols in myocardial tissue proteins to study the oxidative and molecular dynamic
changes after I/R.
After ischemia, blood flow restoration generates an initial oxidative
damage, generated in the mitochondria, that we detected at 20 minutes after
reperfusion. This initial and intracellular oxidative wave consisted on irreversible
monooxidations and affected intracellular proteins essential for cardiac function.
Later, starting at 2h and peaking at 24h after reperfusion, immune cells,
including neutrophils, are recruited to the lesion site as part of the cardiac
inflammatory process. We detected an increase in neutrophil’s granule
peroxidases in the tissue, as well as a second oxidative wave consisting on
irreversible dioxidations and trioxidations and also Cysteine reversible oxidation,
in extracellular and membrane proteins. Towards the end of the first week and
with the start of the repair and fibrotic phase, we detected an increase in collagen
proline-hydroxilations as well as lipid peroxidation accumulation in the tissue.
Additionally, these results were validated in other animal models.
This doctoral thesis provides the first systematic understanding of the
timeline of the different oxidative processes during the first week after I/R. This
study comprises the deep study of the posttranslationally modified peptidome,
the redoxome and the proteome in a highly translational pig model, and might
have implications on the definition of the disease progression and in the prediction and future approaches of the disease.
Files in this item
Size
1.158Mb
Format
Microsoft Excel 2007
Description
Anexo 1. Tabla 1
Size
59.97Kb
Format
Microsoft Excel 2007
Description
Anexo 2. Tabla 2
Size
49.00Kb
Format
Microsoft Excel 2007
Description
Anexo 3. Tabla 3
Size
35.45Kb
Format
Microsoft Excel 2007
Description
Anexo 4. Tabla 4
Size
499.3Kb
Format
Microsoft Excel 2007
Description
Anexo 5. Tabla 5
Size
203.7Kb
Format
Microsoft Excel 2007
Description
Anexo 6. Tabla 6
Size
36.79Kb
Format
Microsoft Excel 2007
Description
Anexo 7. Tabla 7
Size
27.60Kb
Format
Microsoft Excel 2007
Description
Anexo 8. Tabla 8
Size
560.4Kb
Format
Microsoft Excel 2007
Description
Anexo 9. Tabla 9
Size
14.18Kb
Format
Microsoft Excel 2007
Description
Anexo 10. Tabla 10
Size
66.12Kb
Format
Microsoft Excel 2007
Description
Anexo 11. Tabla 11
Size
32.40Kb
Format
Microsoft Excel 2007
Description
Anexo 12. Tabla 12
Size
24.37Kb
Format
Microsoft Excel 2007
Description
Anexo 13. Tabla 13
Size
23.90Kb
Format
Microsoft Excel 2007
Description
Anexo 14. Tabla 14
Size
315.0Kb
Format
Microsoft Excel 2007
Description
Anexo 15. Tabla 15
Size
164.7Kb
Format
Microsoft Excel 2007
Description
Anexo 16. Tabla 16
Size
20.20Kb
Format
Microsoft Excel 2007
Description
Anexo 17. Tabla 17
Google Scholar:Castañs García, Celia
This item appears in the following Collection(s)
Related items
Showing items related by title, author, creator and subject.