INVESTIGADORES
CORTÉS MarÍa Alicia
congresos y reuniones científicas
Título:
High glucose promotes cellular senescense in the kidney by inducing a mild hyperosmolar stress
Autor/es:
MARÍA DEL NOGAL; NURIA TROYANO; JOSE LUIS CANO-PEÑALVER; M. ALICIA CORTÉS; GEMMA OLMOS; SERGIO DE FRUTOS; MANUEL RODRIGUEZ-PUYOL; MARIA P. RUIZ-TORRES
Lugar:
San Diego
Reunión:
Congreso; Kidney Week ASN; 2012
Institución organizadora:
American Society of Nefrology (ASN)
Resumen:
Background: Senescence is a stress response that withdraws the
cell cycle and leads to morphological and functional cellular changes.
Senescence appears in aged and diabetic kidney suggesting an important
role on kidney dysfunction. Our aim was to analyze the role of the
extracellular osmolarity induced by high glucose in human mesangial and
rat kidney cellular senescence and the mechanism involved. Methods:
In order to increase extracellular osmolarity, Human mesangial cells
(HMC) or Ex vivo rat kidney slices were treated with high glucose (HG)
or the control osmolyte mannitol during different periods of time. Male
Wistar rats were treated with mannitol, with streptozotocin to induce
experimental diabetes or with vehicle. Cellular senescence was measured
as β-galactosidase activity using a fluorescent substrate. p53, p21, p16
and Ras expression were measured by immunoblotting and
immunohistochemistry. Ras activation was analyzed by pull down assay.
Reactive oxygen species (ROS) production was evaluated by flow
cytometry. Results: Both HG and mannitol mildly increased
extracellular osmolarity in HMC promoting cellular senescence by
increasing p53, p21 and p16 protein expression. Both HG and Mannitol
promoted an increase in reactive oxygen (ROS) production and the
constitutive activation of Ras, however the inhibition of ROS and Ras
prevented cellular senescence. Both streptozotocin and mannitol rats
shown serum osmolarity and p53 and p16 protein expression increase
compared with controls. Both HG- or mannitol-treated rat kidney slices
shown increased p53 and p16 expression. Conclusions: HG induced
cellular senescence in HMC and rat kidney cortex by inducing
extracellular osmolarity increase, since the control osmolyte mannitol
reproduced the same results. This effect was ROS and Ras dependent.Funding: Government Support - Non-U.S.Course: Annual Meeting: Abstract SessionsSession: Publication Only Abstracts