The induction of drug-metabolizing enzymes by chemicals is one of the major reasons for drug-drug interactions. In the present study, the regulation of mRNA expression of one arylacetamide deacetylase (Aadac) and 11 carboxylesterases (Cess) by 15 microsomal enzyme inducers (MEIs) was examined in livers of male C57BL/6 mice. The data demonstrated that Aadac mRNA expression was suppressed by thre...

BACKGROUND Hypocatabolism of the amyloid beta-protein (Abeta) by insulin-degrading enzyme (IDE) is implicated in the pathogenesis of Alzheimer disease (AD), making pharmacological activation of IDE an attractive therapeutic strategy. However, it has not been established whether the proteolytic activity of IDE can be enhanced by drug-like compounds. METHODOLOGY/PRINCIPAL FINDINGS Based on the ...

We studied plasminogen activator (PA) of the rat pituitary gland in organ and cell monolayer culture. Both anterior and intermediate lobes contain, synthesize and secrete a mixture consisting of the two known types of PA: urokinase and so-called tissue PA. Both enzymes were formed essentially by all PA secreting cells, and PA was identified specifically in mammotrophs, corticotrophs, and lutein...

Angiotensin-converting enzyme 2 (ACE2) is a key renin-angiotensin system enzyme involved in balancing the adverse effects of angiotensin II on the cardiovascular system, and its overexpression by gene transfer is beneficial in cardiovascular disease. Therefore, our objectives were 2-fold: to identify compounds that enhance ACE2 activity using a novel conformation-based rational drug discovery s...

Alkali-activated slag is commonly used as a cement substitute to reduce the environmental footprint of construction materials. Nonetheless, use significant amount alkaline activators, such sodium silicate or hydroxide, can be detrimental in terms global warming potential impact. The aim this work complementary activators partial replacement and therefore activated binder. Calcium calcium carbon...

Proteasomes degrade a multitude of protein substrates in the cytosol and nucleus, and thereby are essential for many aspects of cellular function. Because the proteolytic sites are sequestered in a closed barrel-shaped structure, activators are required to facilitate substrate access. Structural and biochemical studies of two activator families, 11S and Blm10, have provided insights to proteaso...

A method has been developed for accurately and precisely measuring the activity of a range of plasminogen activators (PAs) used as thrombolytic agents, including streptokinase, tissue plasminogen activator (tPA) and variants, and urokinase (uPA), both single and two chain forms. Plasminogen activation is monitored in a transparent, solid fibrin matrix but uses chromogenic substrate hydrolysis, ...

A technique is described for measuring the oxygen uptake of embryonate eggs. Statistical analysis has shown that the method is reliable and accurate. Determinations were made on groups of 15 to 20 eggs, in order to average out individual biological variations. Reduction of the CO(2) tension and relative humidity to approximately zero previous to analysis has been found to be desirable. The oxyg...

The effect of heparin on the activity of lipoprotein lipase from bovine milk was investigated under conditions varying with regard to ionic strength, purity of enzyme, and mode of substrate activation. A crude enzyme (dialyzed skim milk) was studied, along with a purified preparation obtained by affinity chromatography on a column of heparin-substituted agarose. Serum, high density lipoproteins...

The authors reported earlier (1) that the crystalline homoaerine deaminase-cystathionase prepared from rat livers contained pyridoxal-5-phosphate as the prosthetic group, and that the bound pyridoxal-5-phosphate is responsible for the absorption maximum at 427 rnp. The present paper deals with resolution of the enzyme into pyridoxal-5-P and catalytically inactive apoenzyme, and the subsequent r...