The isoprostanes

Jd, Morrow; Lj, Roberts

doi:10.1016/0006-2952(95)02072-1

Cited by 413 publications

(68 citation statements)

References 37 publications

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“…The levels of F2-isoprostanes were determined using gas chromatography/mass spectrometry as described by Morrow and Roberts [25]. The plasma samples obtained from 23 month old mice were added to HPLC (pH 3.0) water and mixed by vortex.…”

Section: Methodsmentioning

confidence: 99%

Continuous overexpression of thioredoxin 1 enhances cancer development and does not extend maximum lifespan in male C57BL/6 mice

Flores

Roman

Cunningham

et al. 2018

Pathobiology of Aging & Age-related Diseases

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We examined the effects of continuous overexpression of thioredoxin (Trx) 1 on aging in Trx1 transgenic mice [Tg(TXN)+/0]. This study was conducted to test whether increased thioredoxin expression over the lifespan in mice would alter aging and age-related pathology because our previous study demonstrated that Tg(act-TXN)+/0 mice had no significant maximum life extension, possibly due to the use of actin as a promoter, which may have resulted in loss of Trx1 overexpression during aging. To test this hypothesis, we generated new Trx1 transgenic mice using a fragment of the human genome containing the TXN gene with an endogenous promoter to ensure continuous overexpression of Trx1 throughout the lifespan. Universal overexpression of Trx1 was observed, and Trx1 overexpression was maintained during aging (up to 22–24 months old) in the Tg(TXN)+/0 mice. The levels of Trx1 are significantly higher (approximately 4 to 31 fold) in all of the tissues examined in the Tg(TXN)+/0 mice compared to the wild-type (WT) littermates. The overexpression of Trx1 did not cause any changes in the levels of Trx2, glutaredoxin, glutathione, or other major antioxidant enzymes. The survival study demonstrated that male Tg(TXN)+/0 mice slightly extended the earlier part of the lifespan compared to WT littermates, but no significant life extension was observed over the lifespan. The cross-sectional pathological analysis (22–25 months old) showed that Tg(TXN)+/0 mice had a significantly higher severity of lymphoma and more tumor burden than WT mice, which was associated with the suppression of the apoptosis signal-regulating kinase 1 (ASK1) pathway. Our findings suggest that the increased levels of Trx1 over the lifespan in Tg(TXN)+/0 mice showed some beneficial effects (slight extension of lifespan) in the earlier part of life but had no significant effects on median or maximum lifespans, and increased Trx1 levels enhanced tumor development in old mice.

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Section: Methodsmentioning

confidence: 99%

Continuous overexpression of thioredoxin 1 enhances cancer development and does not extend maximum lifespan in male C57BL/6 mice

Flores

Roman

Cunningham

et al. 2018

Pathobiology of Aging & Age-related Diseases

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“…2). F 2 -isoprostanes are isomers of PGF 2␣ and have been divided into four structural classes (41)(42)(43). To test their possible affinity for the FP, we selected members of the first (IPF 2␣ -I), third (IPF 2␣ -III), and fourth classes (8-iso-PGF 2␣ , 12-iso-PGF 2␣ , and 9␤, 11␤-PGF 2 ) (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…F 2 isoprostanes are free radical-catalyzed products of arachidonic acid (28). Up to 64 different isomers may be formed theoretically, belonging to four structural classes (41)(42)(43). Initially, these compounds are formed in situ on the cell membrane, from which they may be cleaved by the action of phospholipases to circulate and, ultimately, be excreted in urine (28).…”

Section: Characterization Of the Fp Receptormentioning

confidence: 99%

Functional Characterization of the Ocular Prostaglandin F2α (PGF2α) Receptor

Kunapuli

Lawson

Rokach

et al. 1997

Journal of Biological Chemistry

101

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Prostaglandins are arachidonic acid metabolites that may play a major role as mediators of cellular function. PGF 2␣ 1 has diverse physiological actions ranging from being a potent luteolytic agent (1, 2) to causing smooth muscle contraction in the uterus (3, 4), vasculature (5), and gastrointestinal (6) and respiratory tracts (7,8). PGF 2␣ induces DNA synthesis and cell proliferation in 3T3 fibroblasts (9, 10). Neuronal astrocytes respond to PGF 2␣ , which may mediate pain transmission (11). Recently, PGF 2␣ has also been shown to cause hypertrophy of cardiac myocytes and induction of myofibrillar genes, independent of muscle contraction. These observations suggest a role for the eicosanoid during development, in compensatory hypertrophy and/or in recovery of the heart from injury (12). Recently, PGF 2␣ analogs have been shown to reduce intraocular pressure (IOP), in patients with glaucoma (13,14). Although the precise mechanisms involved remain unclear, the effects of PGF 2␣ analogs on IOP may be attributed, at least in part, to their actions on the ciliary muscle. PGF 2␣ reduces IOP by increasing the uveoscleral outflow of aqueous humor (15, 16), possibly by reducing the resistance between the ciliary muscle bundles, via an effect on the extracellular matrix (17).A single PGF 2␣ receptor (FP) has been cloned from myometrial tissue (18 -22). Given that there is evidence consistent with splice variation of the FP (23), as has been described for other prostanoid receptors (24, 25), we wished to address the possibility that a distinct isoform might mediate the actions of PGF 2␣ in the ciliary muscle. Clarification of the nature of the human ciliary FP and development of an antibody that specifically recognized the receptor protein would facilitate investigation of the effects of PGF 2␣ and its analogs on IOP.PGF 2␣ is formed from arachidonic acid via metabolic transformation sequentially catalyzed by phospholipases, cyclooxygenases, and a specific PGF synthase (26). However, it is now appreciated that a series of PGF 2␣ isomers, the F 2 isoprostanes, may also be formed in vivo via a free radical-dependent pathway (27-29). It has been speculated that these F 2 isoprostanes may function as incidental ligands at eicosanoid receptors, and, possibly, activate related receptors of their own (30). To date, attention has focused particularly on 8-iso-PGF 2␣ . This compound is a potent vasoconstrictor. It is also a mitogen and may activate human platelets (31-33). Curiously, despite its F prostaglandin configuration, 8-iso-PGF 2␣ has been shown to activate thromboxane receptors (TPs), and its biological effects are blocked by TP antagonists (31-33).We now report the cloning of an FP receptor from the human ciliary body (hcb) cDNA library and its localization on the cell membrane. The gene product is identical to that cloned from

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“…Os isoprostanos são uma classe de produtos tóxicos isômeros dos leucotrienos e prostaglandinas e são utilizados como biomarcadores de peroxidação lipídica. Estão presentes em plasma e urina de seres humanos sadios, o que indica que a peroxidação lipídica é um processo que ocorre continuamente [105][106][107][108][109] . .…”

Section: Peroxidação Lipídica E Danos Em Dnaunclassified

Formação de adutos exocíclicos com bases de DNA: implicações em mutagênese e carcinogênese

Loureiro¹,

Mascio²,

Medeiros³

2002

Quím. Nova

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Recebido em 5/7/01; aceito em 28/11/01 EXOCYCLIC DNA ADDUCTS: IMPLICATIONS IN MUTAGENESIS AND CARCINOGENESIS. A number of ring-extended DNA adducts resulting from reaction of a,b-unsaturated aldehydes, or their epoxides, with DNA bases have been characterized in recent years. These adducts can lead to miscoding during DNA replication which, if not repaired, result in mutations that can contribute to cancer development. Recently, the use of ultrasensitive methods allowed the detection of background levels of etheno DNA adducts in tissues of untreated animals and humans suggesting the existence of endogenous sources of reactive intermediates. In this review, we briefly summarize the recent advances in the chemistry of these DNA lesions.Keywords: exocyclic DNA adducts; etheno DNA adducts; lipid peroxidation. INTRODUÇÃOÉ muito antiga a observação de que a exposição dos seres humanos a determinadas substâncias presentes no meio ambiente ou no seu local de trabalho pode levar ao desenvolvimento de câncer. Já no final do século XVIII foi relatado que a ocorrência de câncer de escroto em limpadores de chaminés poderia estar relacionada com a deposição de fuligem e alcatrão nas pregas escrotais. Posteriormente foi mostrado que a aplicação repetida de alcatrão de hulha na pele de animais levava ao eventual desenvolvimento de tumores malignos no sítio da aplicação. Hoje sabemos que o alcatrão de hulha contém hidrocarbonetos aromáticos carcinogênicos, como o benzo[a]pireno. No século XIX foi percebida uma associação entre a exposição de pintores a aminas aromáticas, tal como benzidina, e o desenvolvimento de câncer na bexiga. Somente após 1930 foi demonstrada a associação entre a exposição de animais a diversas aminas aromáti-cas e o desenvolvimento desse tipo de câncer. Atualmente são conhecidas várias substâncias químicas carcinogênicas 1 . Chama-se carcinogênese o processo de conversão de uma célula normal em uma célula maligna, sendo que os agentes indutores desse processo são denominados carcinógenos. Usualmente é necessá-ria a exposição repetida aos carcinógenos para que haja o desenvolvimento de tumores malignos. Esse desenvolvimento ocorre muito lentamente devido à natureza complexa da carcinogênese, a qual pode ser dividida em três estágios: a iniciação, a promoção e a progressão, seqüência de eventos que foi esclarecida no decorrer dos últimos 20 anos 2 . Freqüentemente, após a alteração inicial, aparecem novas populações celulares que representam a evolução de células normais para células pré-neoplásicas, pré-malignas e malignas 3,4 . A iniciação é causada por uma alteração irreversível do DNA, como a reação dessa molécula com substâncias carcinogênicas. Assim, mecanismos de detoxificação de carcinógenos, reparo do DNA e eliminação das células que tenham DNA modificado (por apoptose, por exemplo) são importantes para a proteção contra a iniciação do câncer. Para que a iniciação ocorra, é necessário que haja não só a modificação do DNA, mas também a sua replicação e a proliferação celular, de modo que a mutação in...

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The isoprostanes

Cited by 413 publications

References 37 publications

Continuous overexpression of thioredoxin 1 enhances cancer development and does not extend maximum lifespan in male C57BL/6 mice

Continuous overexpression of thioredoxin 1 enhances cancer development and does not extend maximum lifespan in male C57BL/6 mice

Functional Characterization of the Ocular Prostaglandin F2α (PGF2α) Receptor

Formação de adutos exocíclicos com bases de DNA: implicações em mutagênese e carcinogênese

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