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Oxidative Modification of Rat Sulfotransferase 1A1 Activity in Hepatic Tissue Slices Correlates with Effects on the Purified Enzyme [Articles]

Mammalian cytosolic sulfotransferases (SULTs) catalyze the sulfation of xenobiotics as well as numerous endogenous molecules. The major aryl (phenol) SULT in rat liver, rSULT1A1, has been used extensively as a model enzyme for understanding the catalytic function of SULTs. Previous studies showed that purified rSULT1A1 displays significant catalytic changes in the presence of GSSG and other oxidants. In the present study, the effects of diamide [1,1'-azobis(N,N-dimethylformamide)] and tert-butyl hydroperoxide (TBHP) on the activity of rSULT1A1 in rat hepatic slices were compared with the effects of these oxidants on a homogeneous preparation of the enzyme. Precision-cut hepatic slices were incubated with 10 μM 7-hydroxycoumarin (7-HC) in the presence of varied concentrations of either diamide or TBHP. Analysis of the 7-hydroxycoumarin sulfate released into the incubation medium indicated that both oxidants significantly increased the sulfation of 7-HC, and this occurred at optimal concentrations of 5 and 10 μM, respectively. Cellular GSH and GSSG levels in the hepatic slices were not significantly altered from control values at these concentrations of diamide and TBHP. Exposure of homogeneous rSULT1A1 to diamide or TBHP also increased the rate of sulfation of 7-HC, although the optimal concentrations of diamide and TBHP were lower (50- and 100-fold, respectively) than those required for effects with the hepatic slices. These results indicate that both diamide and TBHP may modify the rSULT1A1 in intact cells in a manner similar to that observed with the homogeneous purified enzyme.

Characterization of a Human Keratinocyte HaCaT Cell Line Model to Study the Regulation of CYP2S1 [Articles]

CYP2S1 is an extrahepatic cytochrome P450 (P450) that shows marked individuality in constitutive and inducible expression. CYP2S1 mRNA expression is increased in psoriasis and by treatments for psoriasis, including retinoids and UV radiation, although endogenous substrates remain poorly characterized. Because previous model systems have overexpressed modified CYP2S1 in bacteria, human HaCaT keratinocyte cells were screened for constitutive and regulatable CYP2S1 expression and CYP2S1 activity in HaCaT cells compared with a novel Chinese hamster ovary (CHO)-based cell line engineered to stably coexpress CYP2S1 and NADPH cytochrome P450 reductase. Constitutive mRNA expression for CYP2S1 and additional P450s, retinoid acid receptors (RARα, RARβ, RAR), and retinoid X receptors (RXRα, RXRβ and RXR) was assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis in HaCaT cells. Cells were then exposed to retinoids or to UV radiation (UVR), and changes in CYP2S1 mRNA abundance were further examined by qRT-PCR analysis. P450 expression in HaCaT cells was similar to human skin, with abundant CYP2S1 expression. RARα and RAR (but not RARβ) and all RXR isoforms were also detectable. All-trans retinoic acid (atRA) induced CYPS1 mRNA expression more potently than 9-cis RA or 13-cis RA. P450-dependent atRA metabolism was demonstrated in HaCaT cells, with a very similar metabolite profile to that produced by our CYP2S1-expressing CHO cells. CYP2S1 mRNA expression was also induced by UVR, more potently than CYP1B1, a known UVR-inducible P450. Our results demonstrate regulatable and functional CYP2S1 expression in HaCaT cells, thus identifying a human cell line model with utility for further analysis of CYP2S1 regulation and substrate specificity.

As A Control Measure During Pandemic Outbreaks, School Closures Should Be Considered
Closing elementary and secondary schools can help slow the spread of infectious disease and should be considered as a control measure during pandemic outbreaks, according to a McMaster University led study. Using high-quality data about the incidence of influenza infections in Alberta during the 2009 H1N1 flu pandemic, the researchers show that when schools closed for the summer, the transmission of infection from person to person was sharply reduced... (Source: Health News from Medical News Today)

Brain Changes Cause Drug Addiction, Researchers Say (LiveScience.com)
LiveScience.com - Drug addicts and their nonaddict siblings share the same brain abnormalities linked with poor self-control and drug dependence, a new study suggests. nbsp;

sulfamethoxazole and trimethoprim, Bactrim, Septra
Title: sulfamethoxazole and trimethoprim, Bactrim, SeptrabrCategory: MedicationsbrCreated: 12/31/1997brLast Editorial Review: 2/2/2012

Parasites Or Not? Transposable Elements In Fruit Flies
Many living organisms suffer from parasites, which use the hosts' resources for their own purposes. The problem of parasitism occurs at all levels right down to the DNA scale. Genomes may contain up to 80% foreign DNA but details of the mechanisms by which this enters the host genome and how hosts attempt to combat its spread are still the subject of conjecture. Important new information comes from the group of Christian Schlotterer at the University of Veterinary Medicine, Vienna. The findings are published in the prestigious journal PLoS Genetics... (Source: Health News from Medical News Today)

The Pathway To Losing Fat Is Heavily Influenced By A Hormone Produced In The Heart
It's well known that exercising reduces body weight because it draws on fat stores that muscle can burn as fuel. But a new study at Sanford-Burnham Medical Research Institute (Sanford-Burnham) suggests that the heart also plays a role in breaking down fat. In their study, published February 6 in the Journal of Clinical Investigation, Sheila Collins, Ph.D. and colleagues detail how hormones released by the heart stimulate fat cell metabolism. These hormones turn on a molecular mechanism similar to what's activated when the body is exposed to cold and burns fat to generate heat... (Source: Health News from Medical News Today)