Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vitamin E was originally considered a dietary factor of animal nutrition especially important for normal reproduction. The significance of vitamin E has been subsequently proven as a radical chain breaking antioxidant that can protect the integrity of tissues and play an important role in life processes. More recently alpha-tocopherol has been found to possess functions that are independent of its antioxidant/radical scavenging ability. Absorption in the body is alpha-tocopherol selective and other tocopherols are not absorbed or are absorbed to a lesser extent. Furthermore, pro-oxidant effects have been attributed to tocopherols as well as an anti-nitrating action. Non-antioxidant and non-pro-oxidant molecular mechanisms of tocopherols have been also described that are produced by alpha-tocopherol and not by beta-tocopherol. alpha-Tocopherol specific inhibitory effects have been seen on protein kinase C, on the growth of certain cells and on the transcription of some genes (CD36, and collagenase). Activation events have been seen on the protein phosphatase PP2A and on the expression of other genes (alpha-tropomyosin and Connective Tissue Growth Factor). Non-antioxidant molecular mechanisms have been also described for gamma-tocopherol, delta-tocopherol and tocotrienols.
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PMID:Vitamin E: non-antioxidant roles. 1079 17

In the last 10 years precise cellular functions of alpha-tocopherol, some of which are independent of its antioxidant/radical-scavenging ability, have been revealed. Absorption of alpha-tocopherol from the gut is a selective process. Other tocopherols are not absorbed or are absorbed to a lesser extent. At the post-translational level, alpha-tocopherol inhibits protein kinase C and 5-lipoxygenase and activates protein phosphatase 2A and diacylglycerol kinase. Some genes [platelet glycoprotein IV/thrombospondin receptor/class B scavenger receptor (CD36), alpha-tocopherol transfer protein (alpha-TTP), alpha-tropomyosin, connective tissue growth factor and collagenase] are affected by alpha-tocopherol at the transcriptional level. alpha-Tocopherol also inhibits cell proliferation, platelet aggregation, monocyte adhesion and the oxygen burst in neutrophils. Other antioxidants, such as beta-tocopherol and probucol, do not mimic these effects, suggesting a nonantioxidant, alpha-tocopherol-specific molecular mechanism.
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PMID:Specific cellular responses to alpha-tocopherol. 1086 30

Most tocopherols and tocotrienols, with the exception of alpha-tocopherol, are not retained by humans. This suggests that alpha-tocopherol is recognized uniquely; therefore, it may exert an exclusive function. alpha-Tocopherol possesses distinct properties that are independent of its prooxidant, antioxidant or radical-scavenging ability. alpha-Tocopherol specifically inhibits protein kinase C, the growth of certain cells and the transcription of the CD36 and collagenase genes. Activation events have also been seen on the protein phosphatase 2A (PP(2)A) and on the expression of other genes (alpha-tropomyosin and connective tissue growth factor). Neither ss-tocopherol nor probucol possessed the same specialty functions as alpha-tocopherol. Recently, we isolated a new ubiquitous cytosolic alpha-tocopherol binding protein (TAP). Its motifs suggest that it is a member of the hydrophobic ligand-binding protein family (CRAL-TRIO). TAP may also be involved in the regulation of cellular alpha-tocopherol concentration and alpha-tocopherol-mediated signaling.
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PMID:Nonantioxidant functions of alpha-tocopherol in smooth muscle cells. 1116 May 65

Recent research on alpha-tocopherol has revealed specific cellular functions of this compound belonging to the vitamin E family. Alpha-tocopherol can act as a radical scavenger, as a pro-oxidant, as an anti-alkylation agent and, most important, by mechanisms that are independent of the above properties. To the last group belong protein kinase C and 5-lipoxygenase inhibition at post-translational level, as well as alpha-tocopherol activation of protein phosphatase 2A and diacylglycerol kinase. Furthermore, at transcriptional level, several genes (CD36, alpha-TTP, alpha-tropomyosin, and collagenase) are modulated by alpha-tocopherol. These effects result in inhibition of smooth muscle cell proliferation, platelet aggregation, and monocyte adhesion and may be related to the alleged protection of atherosclerosis by vitamin E. On the other side, epidemiological and intervention studies have shown some inconsistent results. Rather than disregarding vitamin E as a means to protect against atherosclerosis progression, it would be wiser to better design clinical trials based on current knowledge of the biological properties of the molecule.
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PMID:Vitamin E 80th anniversary: a double life, not only fighting radicals. 1179 98

Molecules provided with an antioxidant function may have additional properties, the latter being sometimes of greater importance than the former. In the last ten years, alpha-tocopherol has revealed precise cellular functions, some of which are independent of its antioxidant/radical scavenging ability. At the posttranslational level, alpha-tocopherol inhibits protein kinase C and 5-lipoxygenase and activates protein phosphatase 2A and diacylglycerol kinase. Some genes (CD36, alpha-TTP, alpha-tropomyosin, and collagenase) are affected by alpha-tocopherol at the transcriptional level. alpha-Tocopherol also induces inhibition of cell proliferation, platelet aggregation and monocyte adhesion. These effects are unrelated to the antioxidant activity of vitamin E, but rather are believed to be a result of specific interactions of vitamin E with components of the cell, e. g. proteins, enzymes and membranes. This review focuses on novel non-antioxidant functions of alpha-tocopherol and discusses the possibility that many of the effects previously attributed to the antioxidant functions can also be explained by non-antioxidant mechanisms.
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PMID:The 80th anniversary of vitamin E: beyond its antioxidant properties. 1203 35

Vitamin E, the most important lipid-soluble antioxidant, was discovered at the University of California at Berkeley in 1922. Since its discovery, studies of the constituent tocopherols and tocotrienols have focused mainly on their antioxidant properties. In 1991 Angelo Azzi's group (Boscoboinik et al. 1991a,b) first described non-antioxidant cell signalling functions for alpha-tocopherol, demonstrating that vitamin E regulates protein kinase C activity in smooth muscle cells. At the transcriptional level, alpha-tocopherol modulates the expression of the hepatic alpha-tocopherol transfer protein, as well as the expression of liver collagen alphal gene, collagenase gene and alpha-tropomyosin gene. Recently, a tocopherol-dependent transcription factor (tocopherol-associated protein) has been discovered. In cultured cells it has been demonstrated that vitamin E inhibits inflammation, cell adhesion, platelet aggregation and smooth muscle cell proliferation. Recent advances in molecular biology and genomic techniques have led to the discovery of novel vitamin E-sensitive genes and signal transduction pathways.
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PMID:Regulation of cell signalling by vitamin E. 1269 Nov 70

Molecules in biological systems often can perform more than one function. In particular, many molecules have the ability to chemically scavenge free radicals and thus act in the test tube as antioxidant, but their main biological function is by acting as hormones, ligands for transcription factors, modulators of enzymatic activities or as structural components. In fact, oxidation of these molecules may impair their biological function, and cellular defense systems exist which protect these molecules from oxidation. Vitamin E is present in plants in 8 different forms with more or less equal antioxidant potential (alpha-, beta-, gamma-, delta-tocopherol/tocotrienols); nevertheless, in higher organisms only alpha-tocopherol is preferentially retained suggesting a specific mechanism for the uptake for this analogue. In the last 20 years, the route of tocopherol from the diet into the body has been clarified and the proteins involved in the uptake and selective retention of alpha-tocopherol discovered. Precise cellular functions of alpha-tocopherol that are independent of its antioxidant/radical scavenging ability have been characterized in recent years. At the posttranslational level, alpha-tocopherol inhibits protein kinase C, 5-lipoxygenase and phospholipase A2 and activates protein phosphatase 2A and diacylglycerol kinase. Some genes (e. g. scavenger receptors, alpha-TTP, alpha-tropomyosin, matrix metalloproteinase-19 and collagenase) are modulated by alpha-tocopherol at the transcriptional level. alpha-Tocopherol also inhibits cell proliferation, platelet aggregation and monocyte adhesion. These effects are unrelated to the antioxidant activity of vitamin E, and possibly reflect specific interactions of alpha-tocopherol with enzymes, structural proteins, lipids and transcription factors. Recently, several novel tocopherol binding proteins have been cloned, that may mediate the non-antioxidant signaling and cellular functions of vitamin E and its correct intracellular distribution. In the present review, it is suggested that the non-antioxidant activities of tocopherols represent the main biological reason for the selective retention of alpha-tocopherol in the body, or vice versa, for the metabolic conversion and consequent elimination of the other tocopherols.
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PMID:Non-antioxidant activities of vitamin E. 1513 10