Hiperosmolaridad y metabolismo lipídico: ¿Son los fosfolípidos y los triglicéridos "moléculas clave" para la adaptación celular a los cambios en la osmolaridad ambiental?
The kidney has an osmolarity gradient along its cortico-medullar axis that is essential for urine concentration. Cells exposed to this high and variable osmolarity must develop protective mechanisms in order to survive in such adverse environment. In the present thesis, we evaluate the role of phosp...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica
2020
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_6710 https://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_6710.dir/6710.PDF |
| Aporte de: |
| Sumario: | The kidney has an osmolarity gradient along its cortico-medullar axis that is essential for urine concentration. Cells exposed to this high and variable osmolarity must develop protective mechanisms in order to survive in such adverse environment. In the present thesis, we evaluate the role of phospholipid and triglyceride metabolism in renal cell survival and adaptation to hyperosmolarity. The experiments shown herein show that hyperosmolar environment increased phospholipid de novo synthesis, which in turn needs an adequate supply of free fatty acids. Free fatty acids de novo synthesis is induced by increasing ACC and FAS expression. As a result, there is an increase in the de novo synthesis of triglycerides and their storage in lipid droplets, which increase in size and number. The study of this lipid dynamics led us to understand how renal cells choose to synthesize phospholipids rather than triglycerides in order to maintain phospholipid renewal and cell membrane homeostasis. This active lipid metabolism observed was a consequence of an increase in the expression of Lipin, DGAT and all PC synthesis enzymes. Also, hyperosmolarity increases cPLA2 pathway and regulates PL, DAG and TAG by controlling lipin and DGAT expression levels. cPLA2 causes AA release, which may act modulating the synthesis pathways in a PG independent manner. Both SREBP and cPLA2 pathway act independently to maintain PL synthesis and survive in this adverse environment. In order to do this, cells produce TAG storage in LD which serve as FFA deposits in order to use them when necessary. Preservation of membrane homeostasis through PL synthesis and renewal is essential in order to maintain cell integrity and constitutes a key protective mechanism for cell survival in hyperosmolarity. |
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