α-Tocopherol as agonist in hypoxia

Mj, Kelly

doi:10.1111/j.2042-7158.1986.tb04471.x

Cited by 11 publications

(4 citation statements)

References 9 publications

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“…Phorbol-12,13-dibutyrate was purchased from Sigma-Aldrich Japan (Tokyo). DL- [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]ornithine hydrochloride (50-62 mCi/ mmol, 50 µCi/ml) and PDBU (10-20 Ci/mmol, 250 µCi/ ml) were obtained from Amersham Life Science (Tokyo). All chemicals were of the highest purity commercially available.…”

Section: Methodsmentioning

confidence: 99%

“…9) Phytol (3,7,11,15-tetramethyl-2-hexadecen-1-ol), the fatty acid side chain of tocopherol, is a branched, longchain aliphatic alcohol contained in large quantities in plants and is a component of chlorophyll. In recent extensive studies, various cellular and biological effects of phytol have been demonstrated, such as its action as an agonist in hypoxia, 10) peroxisome proliferation in skin sebaceous glands 11) and in liver, 12) anti-inflammatory effects, 13) antispasmodic activity, 14) inhibition of efflux of creatine kinase, 15) and reduction of the duration of pentobarbital-induced sleep. 16) Clinically, phytanic acid, which is a derivative of phytol, is associated with Refsum's disease and a phytol-free diet can prevent the progression of that disease.…”

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confidence: 99%

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Phytol Is a Novel Tumor Promoter on ICR Mouse Skin

Kagoura

Matsui

Morohashi

1999

Japanese Journal of Cancer Research

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Phytol is a branched, long-chain aliphatic alcohol which has various biological effects. In this study, we examined phytol as a tumor promoter in a mouse skin initiation-promotion model, and compared its promotion activity with that of 12-O-tetradecanoyl phorbol-13-acetate (TPA). Female ICR mice, 7 weeks of age, were initiated with 100 µ µ µ µg of 7,12-dimethylbenz(a)anthracene, and were then topically promoted twice a week for 16 weeks with 100 mg of phytol or with 2.5 µ µ µ µg of TPA.In this model 95% of animals treated with phytol developed skin tumors within 16 weeks. The average number of lesions per mouse treated with phytol was significantly lower than that in mice treated with TPA, and this significant difference continued up to 16 weeks after the end of promotion treatment. Characterization of hyperplasia 48 h after topical application of agents showed that epidermal thickness and vertical thickness following topical application of phytol were significantly increased compared with vehicle controls, but were significantly smaller than in animals treated with TPA. Ornithine decarboxylase (ODC) activity following topical application of phytol was increased in a dose-dependent manner and showed a weak, delayed induction (which was maximal 11-12 h after treatment) as compared with the case of TPA. The specific binding of [ 3 H]phorbol-12,13-dibutyrate (PDBU) by JB6 cells was not inhibited by phytol at concentrations up to 1 mM. These results indicate that phytol has a weak tumor promoter activity compared to TPA and is a non-TPA-type tumor promoter in this model of mouse skin carcinogenesis. Key words:Phytol -Non-TPA-type tumor promoter -Two-stage mouse skin carcinogenesisOrnithine decarboxylase -Radioligand assay Mouse skin tumorigenesis can be divided into distinct stages of tumor initiation and promotion. According to carcinogenesis experiments, tumor development on mouse skin can be provoked by topical application of an initiator, such as the polycyclic aromatic hydrocarbon 7,12-dimethylbenz(a)anthracene (DMBA), followed by repeated treatment with a tumor promoter.1, 2) Our current understanding of responses to skin tumor promoters has been derived primarily from studies with 12-O-tetradecanoylphorbol-13-acetate (TPA), which affects basal cells but not differentiating cells in mouse epidermis.3) While TPA is the strongest and most widely studied skin tumor promoter, other chemical compounds are known to possess tumorpromoting properties in mouse skin. There have been many reports which have described TPA-type promoters, such as Roussin red methyl ester, 4) and teleocidin, 5) and non-TPA-type promoters, such as okadaic acid, 6) thapsigargin, 7,8) and mirex. 9)Phytol (3,7,11,15-tetramethyl-2-hexadecen-1-ol), the fatty acid side chain of tocopherol, is a branched, longchain aliphatic alcohol contained in large quantities in plants and is a component of chlorophyll. In recent extensive studies, various cellular and biological effects of phytol have been demonstrated, such as its action as an agonist in hypox...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Phytol Is a Novel Tumor Promoter on ICR Mouse Skin

Kagoura

Matsui

Morohashi

1999

Japanese Journal of Cancer Research

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“…Other experiments, using guinea pig colonic smooth muscle, indicate that vitamin K 1 , of a length similar to vitamin E, preserves the smooth muscle functionality during hypoxia [12].…”

Section: Introductionmentioning

confidence: 99%

Vitamin K<sub>1</sub> Prevents the Effect of Hypoxia on Phenylephrine-Induced Contraction in the Carotid Artery

2002

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The purpose of the present study was to investigate the effects of vitamin K₁ on vascular smooth muscle contractility in response to phenylephrine (Phe) during hypoxia. Rat carotid rings were placed in an organ chamber containing Krebs’ solution. The rings were subjected to hypoxia by changing the gas from 95% O₂:5% CO₂ to a mixture containing 95% N₂:5% CO₂. Concentration response curves for Phe were determined before, during, and after exposure to hypoxia. Endothelium-intact rings were incubated with vitamin K₁ for 10 min in normoxic conditions before being subjected to hypoxia. In another set of experiments, endothelium-intact rings were incubated with N^G-nitro-L-arginine methyl ester (L-NAME), indomethacin or a combination of these drugs for 30 min. In endothelium-intact rings, hypoxia caused significant reductions in E_max (from 0.97 ± 0.03 to 0.61 ± 0.04 g/mg; mean ± SEM) and pD₂ values (from 8.26 ± 0.07 to 7.67 ± 0.10). Removal of a functional endothelium effectively prevented the hypoxia-induced reduction in E_max values, but not in pD₂ values (from 9.14 ± 0.10 to 8.70 ± 0.11). Pretreatment with vitamin K₁ at 3 concentrations (5 × 10^–8, 5 × 10^–7, 5 × 10^–6 mol/l) prevented the inhibitory effect of hypoxia in intact rings. Exposure of endothelium-intact rings to L-NAME plus indomethacin also inhibited the hypoxic effect. Our results show that vitamin K₁ prevents the deleterious vascular effects induced by hypoxia, probably due to its action on endothelial cells.

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“…However the chromane ring structure of the vitamin, Trolox, possessing the antioxidant capacity, was not protective and indeed antagonised the action of both vitamin E and phytol. Other experiments, using colonic smooth muscle, indicated that compounds with a phytyl side chain, phytol and vitamin K I , of similar length to vitamin E were active as agonists in hypoxia but compounds that had structural elements resembling the chroniane ring of the vitamin, vitamin K3 and Trolox, were antagonists of these hypoxic responses (Kelly 1986).…”

Section: Discussionmentioning

confidence: 99%

Characteristics of the Protective Action of α‐Tocopherol in Vascular Hypoxia

Richardson

1996

Pharmacology & Toxicology

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The functioning of the guinea-pig isolated portal vein was monitored by measuring spontaneous mechanical activity, responses to electrical stimulation and administered noradrenaline in normoxic conditions. The effect of hypoxia, induced by bubbling the physiological bathing solution with a 95% N(2)/5% CO(2) gas mixture, on the mechanical performance of the vein was then assessed. Spontaneous activity declined in hypoxia, with mean contraction tension reduced by 55 + or - 8.8%. The responses to electrical field stimulation (2-32 Hz, 0.7 msec. 70 V) were lowered by 14 + or - 4.6% but contractions produced by a range of noradrenaline concentrations (0.01-160 mu M) were unaffected by hypoxia. Substitution of glucose in the bathing solution with sucrose, a substrate unavailable to the cells for energy generation, produced a marked enhancement of the effect of hypoxia. Spontaneous activity was reduced by 76 + or - 8.3%, electrically-induced activity by 80 + or - 14.4% and noradrenaline-induced responses by 85 + or - 6.8%. Although in normoxia the activity and responses of the portal vein were unaffected by the presence of alpha-tocopherol, it significantly protected the functioning of the vein in hypoxic conditions. This effect was concentration-dependent within the range 10-160 mu M and was most marked when glucose was replaced by sucrose in the bathing solution.

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α-Tocopherol as agonist in hypoxia

Cited by 11 publications

References 9 publications

Phytol Is a Novel Tumor Promoter on ICR Mouse Skin

Phytol Is a Novel Tumor Promoter on ICR Mouse Skin

Vitamin K<sub>1</sub> Prevents the Effect of Hypoxia on Phenylephrine-Induced Contraction in the Carotid Artery

Characteristics of the Protective Action of α‐Tocopherol in Vascular Hypoxia

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