Publicaciones científicas

Prohibitin deficiency blocks proliferation and induces apoptosis in human hepatoma cells: Molecular mechanisms and functional implications

Sánchez-Quiles V, Santamaría E, Segura V, Sesma L, Prieto J, Corrales FJ.
Division of Hepatology and Gene Therapy, Proteomics Unit, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain

Revista: Proteomics

Fecha: 22-feb-2010

Hepatología

Prohibitin is a multifunctional protein participating in a plethora of essential cellular functions, such as cell signaling, apoptosis, survival and proliferation. In the liver, deficient prohibitin activity participates in the progression of non-alcoholic steatohepatitis and obesity, according to mechanisms that still must be elucidated.

In this study, we have used a combination of transcriptomics and proteomics technologies to investigate the response of human hepatoma PLC/PRF/5 cells to prohibitin silencing to define in detail the biological function of hepatic Phb1 and to elucidate potential prohibitin-dependent mechanisms participating in the maintenance of the transformed phenotype. Abrogation of prohibitin reduced proliferation and induced apoptosis in human hepatoma cells in a mechanism dependent on NFkappaB signaling.

Moreover, down-regulation of ERp29 together with down-regulation of Erlin 2 suggests ER stress. In agreement, increased C/EBP homologous protein levels, poly-ADP ribose polymerase cleavage and activation of caspase 12 and downstream caspase 7 evidenced ER stress-induced apoptosis. Down-regulation of proteasome activator complex subunit 2 and stathmin as well as accumulation of ubiquitinated proteins suggest interplay between ER stress and proteasome malfunction.

Taken together, our results provide evidences for prohibitin having a central role in the maintenance of the transformed and invasive phenotype of human hepatoma cells and may further support previous studies suggesting prohibitin as a potential clinical target.

CITA DEL ARTÍCULO  Proteomics. 2010 Apr;10(8):1609-20

tal vezLE INTERESE

¿QUÉ TECNOLOGÍA UTILIZAMOS?

La Clínica es el hospital privado con mayor dotación tecnológica de España, todo en un único centro.

Imagen de un PET, tecnología de vanguardia en la Clínica Universidad de Navarra

NUESTROS
PROFESIONALES

Los profesionales de la Clínica realizan una labor continuada de investigación y formación, siempre en beneficio del paciente.

Imagen profesionales de la Clínica Universidad de Navarra

POR QUÉ VENIR
A LA CLÍNICA

Conozca por qué somos diferentes a otros centros sanitarios. Calidad, rapidez, comodidad y resultados.

Imagen del edificio de la Clínica Universidad de Navarra