To slow aging => Reduce HIF-1 alpha (?)
Posted by Dr. Anthony G. Payne
“Animals that were designed to over-express HIF-1 did not get the benefit of lifespan extension even though their diets were restricted. Animals that under-expressed HIF-1 lived longer, even when they had a nutrient-rich diet. Furthermore, it was found that the lifespan extension resulting from dietary restriction required activity in signaling pathways in the endoplasmic reticulum, the part of the cell involved in processing and the proper folding of proteins. This finding supports the theory that aging stems from the effects of misfolded proteins and opens up a rich area of investigation to examine the mechanisms by which stress in the endoplasmic reticulum affects lifespan”
Grape seed extract inhibits VEGF expression via reducing HIF-1alpha protein expression.
Department of Molecular Medicine, Beckman Research Institute of the City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
Grape seed extract (GSE) is a widely consumed dietary supplement that has antitumor activity. Here, we have investigated the inhibitory effect of GSE on the expression of vascular endothelial growth factor (VEGF) and the mechanism underlying this action. We found that GSE inhibited VEGF messenger RNA (mRNA) and protein expression in U251 human glioma cells and MDA-MB-231 human breast cancer cells. GSE inhibited transcriptional activation of the VEGF gene through reducing protein but not mRNA expression of hypoxia-inducible factor (HIF) 1alpha. The inhibitory effect of GSE on HIF-1alpha expression was mainly through inhibiting HIF-1alpha protein synthesis rather than promoting protein degradation. Consistent with this result, GSE-suppressed phosphorylation of several important components involved in HIF-1alpha protein synthesis, such as Akt, S6 kinase and S6 protein. Furthermore, in the MDA-MB-231 tumor, we found that GSE treatment inhibited the expression of VEGF and HIF-1alpha and the phosphorylation of S6 kinase without altering the subcellular localization of HIF-1alpha, correlating with reduced vessel density and tumor size. Depletion of polyphenol with polyvinylpyrrolidone abolished the inhibitory activity of GSE, suggesting a water-soluble fraction of polyphenol in GSE is responsible for the inhibitory activity. Taken together, our results indicate that GSE inhibits VEGF expression by reducing HIF-1alpha protein synthesis through blocking Akt activation. This finding provides new insight into the mechanisms of anticancer activity of GSE and reveals a novel molecular mechanism underlying the antiangiogenic action of GSE.
PMID: 19131542 [PubMed – indexed for MEDLINE]
PMCID: PMC2664452 [Available on 2010/04/01]
D-glucosamine down-regulates HIF-1alpha through inhibition of protein translation in DU145 prostate cancer cells.
Chronic Disease Research Center, School of Medicine, Keimyung University, 194 Dongsan-Dong, Jung-Gu, Daegu 700-712, Republic of Korea.
D-glucosamine has been reported to inhibit proliferation of cancer cells in culture and in vivo. In this study we report a novel response to D-glucosamine involving the translation regulation of hypoxia inducible factor (HIF)-1alpha expression. D-glucosamine caused a decreased expression of HIF-1alpha under normoxic and hypoxic conditions without affecting HIF-1alpha mRNA expression in DU145 prostate cancer cells. D-glucosamine inhibited HIF-1alpha accumulation induced by proteasome inhibitor MG132 and prolyl hydroxylase inhibitor DMOG suggesting D-glucosamine reduces HIF-1alpha protein expression through proteasome-independent pathway. Metabolic labeling assays indicated that D-glucosamine inhibits translation of HIF-1alpha protein. In addition, D-glucosamine inhibited HIF-1alpha expression induced by serum stimulation in parallel with inhibition of p70S6K suggesting D-glucosamine inhibits growth factor-induced HIF-1alpha expression, at least in part, through p70S6K inhibition. Taken together, these results suggest that D-glucosamine inhibits HIF-1alpha expression through inhibiting protein translation and provide new insight into a potential mechanism of the anticancer properties of D-glucosamine.
About Dr. Anthony G. PayneMost of the time you will find me spinning ideas and web content for client firms and especially physicians (MDs and DOs). Among my many passions are helping others help others, word weaving (Published writer & author, ghostwriter, copywriter, proofreader, editor), and art (Mainly sketching. I revel in Jackson Pollock's art and thus enjoy experimenting with his approach combined with those of other artists). Nature is a focus too, reflected in the fact I have been involved in the deep ecology movement since the 1980s and (more recently) the Forest Church movement. I am also a Celtic Christian monk (Novice monk in 2015, full monk in 2017). This is the realization of a calling I have "flirted with" for many moons now. You are encouraged to check out my "Summer Cloud's Spiritual Watering Hole" website to learn more: http://summerclouds.weebly.com.
Posted on May 25, 2009, in Diet, DYING & DEATH, Nutrition Science and tagged ANTI-AGING, caloric restriction, D-glucosamine, Grape Seed Extract, HIF-1 alpha, slowing aging. Bookmark the permalink. Comments Off on To slow aging => Reduce HIF-1 alpha (?).
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