tMfn2 gene transfer promotes vascular smooth-muscle cells apoptosis via activation of the mitochondrial cell death pathway.
- Author:
Li ZHAO
1
;
Wei ZHOU
;
Si-kun WANG
;
Hua LIAO
;
Wen-juan ZHANG
;
Guang-hui CHEN
;
Xiao-mei GUO
Author Information
- Publication Type:Journal Article
- MeSH: Adenoviridae; Animals; Apoptosis; Caspase 9; metabolism; Cells, Cultured; Membrane Proteins; genetics; Mitochondria; metabolism; Mitochondrial Membranes; metabolism; Mitochondrial Proteins; genetics; Muscle, Smooth, Vascular; cytology; metabolism; Myocytes, Smooth Muscle; metabolism; Proto-Oncogene Proteins c-akt; metabolism; Proto-Oncogene Proteins c-bcl-2; metabolism; Rats; Transfection; bcl-2-Associated X Protein; metabolism
- From: Chinese Journal of Cardiology 2009;37(7):639-643
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effect of tMfn2 gene transfer on promoting the apoptosis of vascular smooth-muscle cells (VSMCs).
METHODSVSMCs were infected by adenovirus-mediated tMfn2 (Adv-tMfn2) or adenovirus-mediated Mfn2 (Adv-Mfn2). FACS analysis, cell death ELISA and TUNEL staining were used to investigate the role of tMfn2 and Adv-Mfn2 gene transfer on VSMCs apoptosis. Western blot was used to analyze the protein expression of p-Akt, Bcl-2, Bax and cleaved caspase-9.
RESULTSFACS and ELISA results showed that tMfn2 was superior to Mfn2 in promoting VSMCs apoptosis and tMfn2 gene transfer induced VSMCs apoptosis in a time-dependent manner (P < 0.01). TUNEL staining evidenced that there were more positive-apoptotic VSMCs in tMfn2 group than that in Mfn2 group (P < 0.01). The protein expressions of phosphorylated Akt and Bcl-2 were significantly decreased, whereas Bax and cleaved caspase-9 protein expressions were significantly upregulated in tMfn2-transfected VSMCs.
CONCLUSIONStMfn2 transfer promoted apoptosis of VSMCs in a time dependent manner via the PI3K-Akt signaling pathway and mitochondrial apoptotic pathway.
