Sex differences in hepatic gene expression in a rat model of ethanol-induced liver injury

Tadić, Staša; Elm, Mary S.; Li, Ha-Sheng; Londen, G J. Van; Субботин, Владимир; Whitcomb, David C.; Eagon, Patricia K.

doi:10.1152/japplphysiol.00568.2001

Cited by 44 publications

(30 citation statements)

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“…In downregulatory genes Lsdh and CYP2C11 expression were reduced as expected after ethanol consumption (Figure 4; Tadic et al, 2002;Deaciuc et al, 2004a). Thus, similar results of alcohol related gene expression were obtained employing two independent detection techniques and established that ethanol exposure elicits stable changes in gene expression both in primary hepatocytes culture as well as liver invivo (present study and Deaciuc et al, 2004a,b).…”

Section: Ethanol Induced Changes In Genes Expressed In Liversupporting

confidence: 86%

“…Nearly 35% of genes expressed in liver exhibit more than two fold changes in the presence of ethanol (Deaciuc et al, 2004a). Using same gene chip approach, other studies have confirmed a similar trend of alcohol induced gene expression (Tadic et al, 2002;Deaciuc et al, 2004b;French et al, 2005). To validate this ethanol sensitivity we selected four genes; two genes that are upregulated, [Alcohol dehydrogennase-1 (Adh-1) and GlutathionS-transferase Yc2 (GST-Yc2)], and two genes that are downregulated, [L-serine dehydratase (Lsdh) and Cytochrome P450 2C11 (CYP2C11)], by ethanol (Tadic et al, 2002;Park et al, 2005).…”

Section: Ethanol Induced Changes In Genes Expressed In Livermentioning

confidence: 55%

“…Prolonged exposure to ethanol impairs liver function via different pathways and exhibits global change in hepatic gene expression covering a wide spectrum of cellular function (Tadic et al, 2002;Deaciuc et al, 2004a,b;French et al, 2005). Thus changes in the expression of genes have been implicated in the development of alcoholic liver diseases (ALD).…”

Section: Introductionmentioning

confidence: 99%

“…Genes that are involved in ethanol metabolism (Morimoto et al, 1993;Ronis et al, 1993;Deaciuc et al, 2004a,b) cell signaling (Mochly-Rosen et al, 1988;Gordon et al, 1986;Hong et al, 2002a,b) and apoptosis (Yacoub et al, 1995;Deaciuc et al, 1999;Deaciuc et al, 2002a,b;Koteish et al, 2002) are highly sensitive to alcohol. Micro-array studies have also shown profile of hepatic gene expressions induced by alcohol consumption (Tadic et al, 2002;Deaciuc et al, 2004a,b;French et al, 2005). These changes in liver transcriptomes affect different transcriptional factors, enzymes of several metabolic pathways, receptors, cytokines, signaling molecules, immuno-modulators, antioxidant enzymes and modifiers of proteins secretors etc.…”

Section: Introductionmentioning

confidence: 99%

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Distinct methylation patterns in histone H3 at Lys-4 and Lys-9 correlate with up- & down-regulation of genes by ethanol in hepatocytes

et al. 2007

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Ethanol induced liver injury is associated with a global change in gene expression but its mechanisms are not known. We studied whether alcohol induced gene expression are associated with posttranslational methylations of histone H3. Primary culture of rat hepatocytes were treated with ethanol (50 or 100 mM) for 24 hr and the status of methylation of H3 at lys 4 (H3dimeK4) or lys 9 (H3dimeK9) were monitored by western blotting using antibodies to dimethylated histone H3 at lys 4 or lys 9. The cells exposed to ethanol showed strikingly opposing behaviors in methylation patterns; H3dimeK9 methylation was decreased whereas H3dimeK4 increased. Similar results were obtained in the interphase nuclei. Their binding on the metaphase chromosomes exhibit distinct site specific pattern of accumulation. Next, chromatin immuno-precipitation of the ethanol treated samples with antibodies for methylated lys 4 or lys 9 histone H3 followed by amplification of the immunoprecipitated DNA, was used to determine their association with the promoters of genes up-or down regulated by ethanol. Lys4 methylation was associated with ethanol up-regulated genes (Adh, GSTyc2) whereas lys 9 methylation with down regulated genes (Lsdh, cytP4502c11) demonstrating a difference between these two methylations. These results suggest that exposure of hepatocytes to ethanol changes the expression of several susceptible genes which are associated with site specific modification of dimethylated forms of histone H3 amino termini at their regulatory regions.

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Section: Ethanol Induced Changes In Genes Expressed In Liversupporting

confidence: 86%

Section: Ethanol Induced Changes In Genes Expressed In Livermentioning

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Distinct methylation patterns in histone H3 at Lys-4 and Lys-9 correlate with up- & down-regulation of genes by ethanol in hepatocytes

et al. 2007

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“…Interestingly, gender-specific gene expression in the mouse brain is found at an embryonic stage that precedes the production of sex hormones [17]. Other cases of gender divergence in gene expression include the hepatic response to ethanol consumption in rats [18], and the sensitivity of murine hematopoietic stem cells to benzene intoxication [19]. An example of gender difference in the heart includes the genomic response to pressure overload, a condition in which male mice show a more robust over-expression of genes involved in immunity and inflammation than females [20], which is in agreement with the more pronounced inflammatory response found in male mice after MI as described here by Fang et al [2].…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Sex differences in myocardial infarction and rupture

Qiu

Depré

Vatner

et al. 2007

Journal of Molecular and Cellular Cardiology

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Although myocardial rupture occurs in a relatively low percentage (2-4%) of cases of acute myocardial infarction (MI), it is associated with an extremely high mortality rate due to cardiogenic shock (up to 90% in cases of free wall rupture and 50% of cases involving septal rupture), and it accounts for up to 25% of in-hospital death [1]. Understanding the molecular mechanisms leading to myocardial rupture therefore represents an important challenge for improving the short term prognosis of MI. In the present issue of the Journal, Fang and coauthors [2] investigate an intriguing aspect of the pathophysiology of this disease, which relates to the mechanisms underlying the gender differences in the rate of post-MI rupture.It is well documented that the incidence of acute MI varies according to both gender and age. The Framingham study, for example, has demonstrated that the incidence of acute MI is 2.5-fold higher in males than females before age 45, however, this gender difference disappears after 55 years of age [3]. Clinical studies indicate that the rate of acute mortality, including sudden death, in men is about twice that observed in women [4]. This poorer prognosis in men is also supported by the observation that myocardial rupture after MI is observed twice as often in men than in women [5]. The prognosis of MI is also usually worse in younger patients due to the absence of a history of chronic ischemia and secondary collateral development, and because an early MI is usually due to the accumulation of several risk factors, such as diabetes, smoking, metabolic syndrome and consumption of recreational drugs [6].These clinical observations of sex differences in the incidence and the prognosis of acute cardiovascular events correlate with several studies conducted in large mammals [7][8][9][10]. In a monkey model of aging, gender differences in gene and protein expression can explain several aspects of the characteristic protection of females against cardiovascular disease, including a better preservation with aging of the expression of enzymes of glycolytic and oxidative pathways [10], a better cardiovascular response to β-adrenergic stimulation [9], less apoptosis and myocyte hypertrophy in old female monkeys than in old male monkeys [11], as well as differences in the composition of the extracellular matrix of conductance vessels, such as elastin and collagen isoforms, which correlates with lower vascular stiffness in females compared to males [7,8]. Some of these differences between males and females are already present at a young age, especially for genes expressed on sex chromosomes, suggesting that gender differences in expression of genes and proteins in the cardiovascular system can already be programmed early in life [8]. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof be...

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Unravelling Sex Differences in Drug‐Induced Liver Injury

Tong

Shi

Salminen

et al. 2009

General, Applied and Systems Toxicology

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Liver toxicity accounts for 40% of failed drugs in clinical studies and approximately 21% of drugs that are removed from the market. It is suspected that drug‐induced liver injury (DILI) is more common in females, thus impacting women's health to a higher degree. However, it is unclear how common this potential sex‐based sensitivity may be and the mechanisms underlying the differences. High‐content and high‐throughput molecular technologies such as DNA microarrays have contributed significantly to the understanding of health and disease at the molecular level. In 2001, DNA microarray studies began to emerge to investigate sex‐associated liver gene expression profiles under physiological and pathological conditions. This review is an analysis of clinical reports published to date to determine the weight of evidence in support of sex‐biased sensitivity to DILI. Sex differences related to disease susceptibility/progression and adverse drug events are discussed at the molecular level with emphasis on genomic data in an attempt to place the evidence in a biological context.

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Sex differences in hepatic gene expression in a rat model of ethanol-induced liver injury

Abstract: . Sex differences in hepatic gene expression in a rat model of ethanol-induced liver injury.

Cited by 44 publications

References 58 publications

Distinct methylation patterns in histone H3 at Lys-4 and Lys-9 correlate with up- & down-regulation of genes by ethanol in hepatocytes

Distinct methylation patterns in histone H3 at Lys-4 and Lys-9 correlate with up- & down-regulation of genes by ethanol in hepatocytes

Sex differences in myocardial infarction and rupture

Unravelling Sex Differences in Drug‐Induced Liver Injury

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