Inhibition of Mitochondrial Cytochrome c Release and Suppression of Caspases by Gamma-Tocotrienol Prevent Apoptosis and Delay Aging in Stress-Induced Premature Senescence of Skin Fibroblasts
Joint Authors
Makpol, Suzana
Kien Hui, Chua
Ngah, Wan Zurinah Wan
Abdul Rahim, Norhazira
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-07-22
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Natural & Life Sciences (Multidisciplinary)
Biology
Abstract EN
In this study, we determined the molecular mechanism of γ-tocotrienol (GTT) in preventing cellular aging by focusing on its anti-apoptotic effect in stress-induced premature senescence (SIPS) model of human diploid fibroblasts (HDFs).
Results obtained showed that SIPS exhibited senescent-phenotypic characteristic, increased expression of senescence-associated β-galactosidase (SA β-gal) and promoted G0/G1 cell cycle arrest accompanied by shortening of telomere length with decreased telomerase activity.
Both SIPS and senescent HDFs shared similar apoptotic changes such as increased Annexin V-FITC positive cells, increased cytochrome c release and increased activation of caspase-9 and caspase-3 (P<0.05).
GTT treatment resulted in a significant reduction of Annexin V-FITC positive cells, inhibited cytochrome c release and decreased activation of caspase-9 and caspase-3 (P<0.05).
Gene expression analysis showed that GTT treatment down regulated BAX mRNA, up-regulated BCL2A1 mRNA and decreased the ratio of Bax/Bcl-2 protein expression (P<0.05) in SIPS.
These findings suggested that GTT inhibits apoptosis by modulating the upstream apoptosis cascade, causing the inhibition of cytochrome c release from the mitochondria with concomitant suppression of caspase-9 and caspase-3 activation.
In conclusion, GTT delays cellular senescence of human diploid fibroblasts through the inhibition of intrinsic mitochondria-mediated pathway which involved the regulation of pro- and anti-apoptotic genes and proteins.
American Psychological Association (APA)
Makpol, Suzana& Abdul Rahim, Norhazira& Kien Hui, Chua& Ngah, Wan Zurinah Wan. 2012. Inhibition of Mitochondrial Cytochrome c Release and Suppression of Caspases by Gamma-Tocotrienol Prevent Apoptosis and Delay Aging in Stress-Induced Premature Senescence of Skin Fibroblasts. Oxidative Medicine and Cellular Longevity،Vol. 2012, no. 2012, pp.1-13.
https://search.emarefa.net/detail/BIM-497948
Modern Language Association (MLA)
Makpol, Suzana…[et al.]. Inhibition of Mitochondrial Cytochrome c Release and Suppression of Caspases by Gamma-Tocotrienol Prevent Apoptosis and Delay Aging in Stress-Induced Premature Senescence of Skin Fibroblasts. Oxidative Medicine and Cellular Longevity No. 2012 (2012), pp.1-13.
https://search.emarefa.net/detail/BIM-497948
American Medical Association (AMA)
Makpol, Suzana& Abdul Rahim, Norhazira& Kien Hui, Chua& Ngah, Wan Zurinah Wan. Inhibition of Mitochondrial Cytochrome c Release and Suppression of Caspases by Gamma-Tocotrienol Prevent Apoptosis and Delay Aging in Stress-Induced Premature Senescence of Skin Fibroblasts. Oxidative Medicine and Cellular Longevity. 2012. Vol. 2012, no. 2012, pp.1-13.
https://search.emarefa.net/detail/BIM-497948
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-497948