Molecular basis of α‐tocopherol control of smooth muscle cell proliferation

Azzi, Angelo; Aratri, Elisabetta; Boscoboinik, Daniel; Clément, Sophie; Özer, Nesrin Kartal; Ricciarelli, Roberta; Spycher, Stefan

doi:10.1002/biof.5520070102

Cited by 93 publications

(65 citation statements)

References 26 publications

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“…In fact, in cholesterol fed rabbits a-tocopherol is able to suppress the cholesterol-induced increase of CD36 in aorta (Azzi et al, unpublished results). (Azzi et al, 1998a;Aratri et al, 1999). Furthermore, a number of studies have linked the effects of tocopherol with events related with the regulation of connective tissue proteins, collagen expression and fibrogenesis.…”

Section: Group 2: Regulation Of Genes That Are Involved In Lipid Uptamentioning

confidence: 99%

Regulation of gene expression by α-tocopherol

Azzi¹,

Gysin²,

Kempná³

et al. 2004

Biological Chemistry

127

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Section: Group 2: Regulation Of Genes That Are Involved In Lipid Uptamentioning

confidence: 99%

Regulation of gene expression by α-tocopherol

Azzi¹,

Gysin²,

Kempná³

et al. 2004

Biological Chemistry

127

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“…No doubt they are vital cogs in numerous metabolic reactions and are co players in redox homeostasis [21][22][23][24][25] but then are many others cellular molecules of equal importance. Further,many AO perform equally or even more important of non-antioxidant duties [20,26,27].The examples are role of vitamin A in vision [28], vitamin C in collagen synthesis [29][30][31][32][33] and vitamin E in smooth muscle cell proliferation endothelial dysfunction platelet aggregation by a protein kinase C dependent mechanism and tumor suppression [26,[34][35][36].…”

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confidence: 99%

Reconvene and Reconnect the Antioxidant Hypothesis in Human Health and Disease

Singh

Chandra

Mahdi

et al. 2010

Indian J Clin Biochem

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The antioxidants are essential molecules in human system but are not miracle molecules. They are neither performance enhancers nor can prevent or cure diseases when taken in excess. Their supplemental value is debateable. In fact, many high quality clinical trials on antioxidant supplement have shown no effect or adverse outcomes ranging from morbidity to all cause mortality. Several Chochrane Meta-analysis and Markov Model techniques, which are presently best available statistical models to derive conclusive answers for comparing large number of trials, support these claims. Nevertheless none of these statistical techniques are flawless. Hence, more efforts are needed to develop perfect statistical model to analyze the pooled data and further double blind, placebo controlled interventional clinical trials, which are gold standard, should be implicitly conducted to get explicit answers. Superoxide dismutase (SOD), glutathione peroxidase and catalase are termed as primary antioxidants as these scavenge superoxide anion and hydrogen peroxide. All these three enzymes are inducible enzymes, thereby inherently meaning that body increases or decreases their activity as per requirement. Hence there is no need to attempt to manipulate their activity nor have such efforts been clinically useful. SOD administration has been tried in some conditions especially in cancer and myocardial infarction but has largely failed, probably because SOD is a large molecule and can not cross cell membrane. The dietary antioxidants, including nutrient antioxidants are chain breaking antioxidants and in tandem with enzyme antioxidants temper the reactive oxygen species (ROS) and reactive nitrogen species (RNS) within physiological limits. Since body is able to regulate its own requirements of enzyme antioxidants, the diet must provide adequate quantity of non-enzymic antioxidants to meet the normal requirements and provide protection in exigent condition. So far, there is no evidence that human tissues ever experience the torrent of reactive species and that in chronic conditions with mildly enhanced generation of reactive species, the body can meet them squarely if antioxidants defense system in tissues is biochemically optimized. We are not yet certain about optimal levels of antioxidants in tissues. Two ways have been used to assess them: first by dietary intake and second by measuring plasma levels. Lately determination of plasma/serum level of antioxidants is considered better index for diagnostic and prognostic purposes. The recommended levels for vitamin A, E and C and beta carotene are 2.2-2.8 lmol/l; 27.5-30 lmol/l; 40-50 lmol/l and 0.4-0.5 lmol/l, respectively. The requirement and recommended blood levels of other dietary antioxidants are not established. The resolved issues are (1) essential to scavenge excess of radical species (2) participants in redox homeostasis (3) selective antioxidants activity against radical species (4) there is no universal antioxidant and 5) therapeutic value in case of deficiency. The overar...

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“…16) Antioxidants, including alpha-tocopherol, inhibit proliferation of many types of cells such as vascular smooth muscle, 17) fibroblasts, 18) and various cancer cell lines, 19) In the present study, Y-700 effectively suppressed the development of DMH-induced ACF associated with cell proliferation of colonic mucosa. These findings suggest that ROS generated by XO might act as important mediators of mitogenic signaling in colon cancer.…”

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confidence: 48%