Activation of PKCδ and ERK1/2 in the Sensitivity to UV-Induced Apoptosis of Human Cells Harboring 4977 bp Deletion of Mitochondrial DNA - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Biochimica et Biophysica Acta - Molecular Basis of Disease Année : 2009

Activation of PKCδ and ERK1/2 in the Sensitivity to UV-Induced Apoptosis of Human Cells Harboring 4977 bp Deletion of Mitochondrial DNA

Résumé

The 4977 bp deletion of mitochondrial DNA (mtDNA), often found in patients with chronic progressive external ophthalmoplegia (CPEO), has been demonstrated to increase the susceptibility to apoptosis of human cells. We investigated the mechanism underlying the apoptotic susceptibility of the △4977 cybrid harboring about 80% 4977 bp-deleted mtDNA. The production of hydrogen peroxide (HO) and phosphorylation of PKCδ and ERK1/2 were increased in the △4977 cybrid, which was more susceptible to UV-induced apoptosis. Moreover, treatment with N-acetyl-L-cysteine (NAC) or blocking of activation of PKCδ by rottlerin or PKCδ-siRNA, and inhibition of ERK1/2 by PD98059 or ERK1/2-siRNA significantly attenuated the susceptibility of the △4977 cybrid to apoptosis. Furthermore, the increase of PKCδ expression in the △4977 cybrid also amplified the apoptotic signal through caspase 3-mediated proteolytic activation of PKCδ. In addition, PKCδ and ERK1/2 were hyperphosphorylated in skin fibroblasts of CPEO patients harboring 4977 bp-deleted mtDNA. We suggest that the activation of PKCδ and ERK1/2 elicited by 4977 bp-deleted mtDNA-induced oxidative stress plays a role in the susceptibility of the mutant cells to apoptosis. This may explain, at least in part, the degenerative manifestation of brain and muscle in patients with mitochondrial encephalomyopathies such as CPEO syndrome.
Fichier principal
Vignette du fichier
PEER_stage2_10.1016%2Fj.bbadis.2009.05.005.pdf (553.19 Ko) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...

Dates et versions

hal-00562906 , version 1 (04-02-2011)

Identifiants

Citer

Chun-Yi Liu, Cheng-Feng Lee, Yau-Huei Wei. Activation of PKCδ and ERK1/2 in the Sensitivity to UV-Induced Apoptosis of Human Cells Harboring 4977 bp Deletion of Mitochondrial DNA. Biochimica et Biophysica Acta - Molecular Basis of Disease, 2009, 1792 (8), pp.783. ⟨10.1016/j.bbadis.2009.05.005⟩. ⟨hal-00562906⟩

Collections

PEER
58 Consultations
95 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More