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Post by Max on Jul 17, 2005 17:00:13 GMT -5
The statistical life-expectancy of subjects exposed to (Ro)accutane is not known. A statistically significant effect on life expectancy can not be excluded.
Suggested loss of stem-cells due to apoptosis
Significantly increased risk factors for premature aging induced by (Ro)accutane
Possible adult mutations, high dose retinoic acid induced DNA instability and accelerated aging
Laminopathies are a group of diseases due to mutations of type A-lamins, a group of proteins lining the inner aspect of cell nuclei [1]. Laminopathies have been found to accelerate aging due to defiecent DNA repair [3]. The lamin A promoter contains a responsive element for retinoic acid (L-RARE) and is thus affected during exposure of (Ro)accutane [2]. Recruitment of p53 binding protein 1 (53BP1) and Rad51 to sites of DNA lesion is impaired in Zmpste24(-/-) MEFs and in HGPS fibroblasts, resulting in delayed checkpoint response and defective DNA repair [3]. High p53 protein expression (LI >/= 0.2) was detected in 25% of the lesions at baseline and in 18% of the lesions after isotretinoin exposure [4].
Possible effect on telomeres
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Post by Max on Jul 20, 2005 6:15:47 GMT -5
Free Radic Biol Med. 2001 Dec 1;31(11):1287-312. Related Articles, Links
Reactive oxygen species, antioxidants, and the mammalian thioredoxin system.
Nordberg J, Arner ES.
Medical Nobel Institute for Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Reactive oxygen species (ROS) are known mediators of intracellular signaling cascades. Excessive production of ROS may, however, lead to oxidative stress, loss of cell function, and ultimately apoptosis or necrosis. A balance between oxidant and antioxidant intracellular systems is hence vital for cell function, regulation, and adaptation to diverse growth conditions. Thioredoxin reductase (TrxR) in conjunction with thioredoxin (Trx) is a ubiquitous oxidoreductase system with antioxidant and redox regulatory roles. In mammals, extracellular forms of Trx also have cytokine-like effects. Mammalian TrxR has a highly reactive active site selenocysteine residue resulting in a profound reductive capacity, reducing several substrates in addition to Trx. Due to the reactivity of TrxR, the enzyme is inhibited by many clinically used electrophilic compounds including nitrosoureas, aurothioglucose, platinum compounds, and retinoic acid derivatives. The properties of TrxR in combination with the functions of Trx position this system at the core of cellular thiol redox control and antioxidant defense. In this review, we focus on the reactions of the Trx system with ROS molecules and different cellular antioxidant enzymes. We summarize the TrxR-catalyzed regeneration of several antioxidant compounds, including ascorbic acid (vitamin C), selenium-containing substances, lipoic acid, and ubiquinone (Q10). We also discuss the general cellular effects of TrxR inhibition. Dinitrohalobenzenes constitute a unique class of immunostimulatory TrxR inhibitors and we consider the immunomodulatory effects of dinitrohalobenzene compounds in view of their reactions with the Trx system.
Publication Types:
Review
Review, Tutorial
PMID: 11728801 [PubMed - indexed for MEDLINE]
Atherosclerosis. 2005 Jul 23; [Epub ahead of print] Related Articles, Links
Oxidized LDL induces a coordinated up-regulation of the glutathione and thioredoxin systems in human macrophages.
Hagg D, Englund MC, Jernas M, Schmidt C, Wiklund O, Hulten LM, Ohlsson BG, Carlsson LM, Carlsson B, Svensson PA.
Research Centre for Endocrinology and Metabolism, Division of Body Composition and Metabolism, Department of Internal Medicine, Vita straket 15, Sahlgrenska University Hospital, S-413 45 Goteborg, Sweden.
Using DNA microarray analysis, we found that human macrophages respond to oxidized low-density lipoprotein (oxLDL) by activating the antioxidative glutathione and thioredoxin systems. Several genes of the glutathione and thioredoxin systems were expressed at high levels in macrophages when compared to 80 other human tissues and cell types, indicating that these systems may be of particular importance in macrophages. The up-regulation of three genes in these systems, thioredoxin (P<0.005), thioredoxin reductase 1 (P<0.001) and glutathione reductase (P<0.001) was verified with real-time RT-PCR, using human macrophages from 10 healthy donors. To investigate the possible role of these antioxidative systems in the development of atherosclerosis, expression levels in macrophages from 15 subjects with atherosclerosis (12 men, 3 women) and 15 matched controls (12 men, 3 women) were analyzed using DNA microarrays. Two genes in the glutathione system Mn superoxide dismutase (P<0.05) and catalase (P<0.05) differed in expression between the groups. We conclude that macrophage uptake of oxidized LDL induces a coordinated up-regulation of genes of the glutathione and thioredoxin systems, suggesting that these systems may participate in the cellular defense against oxidized LDL and possibly modulate the development of atherosclerosis.
PMID: 16046214 [PubMed - as supplied by publisher]
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Post by Max on Jul 20, 2005 6:25:28 GMT -5
References:
[1] Vigouroux C. [Laminopathies: lipodystrophies, insulin resistance, syndromes of accelerated ageing... and others] (2005) Ann Endocrinol (Paris). Jun;66(3):270-8.
[2] Okumura K, Hosoe Y, Nakajima N. c-Jun and Sp1 family are critical for retinoic acid induction of the lamin A/C retinoic acid-responsive element. (2004) Biochem Biophys Res Commun. Jul 23;320(2):487-92.
[3] Liu B, Wang J, Chan KM, Tjia WM, Deng W, Guan X, Huang JD, Li KM, Chau PY, Chen DJ, Pei D, Pendas AM, Cadinanos J, Lopez-Otin C, Tse HF, Hutchison C, Chen J, Cao Y, Cheah KS, Tryggvason K, Zhou Z.
Genomic instability in laminopathy-based premature aging. (2005) Nat Med. Jul;11(7):780-5.
[4] Shin DM, Xu XC, Lippman SM, Lee JJ, Lee JS, Batsakis JG, Ro JY, Martin JW, Hittelman WN, Lotan R, Hong WK. Accumulation of p53 protein and retinoic acid receptor beta in retinoid chemoprevention.
(1997) Clin Cancer Res. Jun;3(6):875-80.
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Post by fghjhgf on Sept 7, 2018 19:58:04 GMT -5
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