Pharmacological inhibition of SIRT-2 by AK-7 modulates redox status and apoptosis via regulating Nrf2 in an experimental model of chronic obstructive pulmonary disease: an invivo and insilico study.

Chronic obstructive pulmonary disease (COPD) is defined by inflammation and emphysema. Sirtuins (SIRT) are NAD-dependent histone deacetylases that regulate oxidative stress and inflammation. The present work investigates the modulatory role of SIRT-2 in experimental COPD model.

Colorimetric detection of Escherichia coli using engineered bacteriophage and an affinity reporter system.

Reporter phage systems have emerged as a promising technology for the detection of bacteria in foods and water. However, the sensitivity of these assays is often limited by the concentration of the expressed reporter as well as matrix interferences associated with the sample. In this study, bacteriophage T7 was engineered to overexpress mutated alkaline phosphatase fused to a carbohydrate-binding module (ALP*-CBM) following infection of E.

A phage-based assay for the rapid, quantitative, and single CFU visualization of E. coli (ECOR #13) in drinking water.

Drinking water standards in the United States mandate a zero tolerance of generic E. coli in 100 mL of water. The presence of E.

Antioxidant potential of Phyllanthus fraternus Webster on cyclophosphamide induced changes in sperm characteristics and testicular oxidative damage in mice.

Cyclophasphamide (CPA) is used to treat various types of cancer. It is a cytotoxic alkylating agent widely used in chemotherapeutic regimen. However, the clinical efficacy of CPA is marred by its side effects.

Evaluation of the antioxidant and hepatoprotective effect of Phyllanthus fraternus against a chemotherapeutic drug cyclophosphamide.

In the present study, hepatoprotective and antioxidant properties of aqueous extract of Phyllanthus fraternus (AEPF 200, 300, and 400 mg/kg body weight (bw), orally) were investigated against cyclophosphamide (CPA 200 mg/kg, bw, intraperitoneally administered) induced liver damage in mice. Histopathological studies of CPA administration cause liver injury, featuring substantial increase in serum glutamic oxaloacetic transaminase, serum glutamate pyruvate transaminase, lactate dehydrogenase, alkaline phosphatase, acid phosphatase, and total bilirubin. Moreover, CPA intoxication also causes strong oxidative stress, which is evident from significant increase in lipid peroxide level.

Cellular responses to misfolded proteins and protein aggregates.

Maintenance of the proteome is a major homeostatic task of the cell and disregulation of protein homeostasis can be deadly. The accumulation of different forms of misfolded protein can perturb protein homeostasis and cause extensive cell and tissue damage. The cell has various quality control systems to help prevent the accumulation of misfolded proteins and the complexity of the different mechanisms that have evolved is bewildering.

PLP-dependent H(2)S biogenesis.

The role of endogenously produced H(2)S in mediating varied physiological effects in mammals has spurred enormous recent interest in understanding its biology and in exploiting its pharmacological potential. In these early days in the field of H(2)S signaling, large gaps exist in our understanding of its biological targets, its mechanisms of action and the regulation of its biogenesis and its clearance. Two branches within the sulfur metabolic pathway contribute to H(2)S production: (i) the reverse transsulfuration pathway in which two pyridoxal 5'-phosphate-dependent (PLP) enzymes, cystathionine β-synthase and cystathionine γ-lyase convert homocysteine successively to cystathionine and cysteine and (ii) a branch of the cysteine catabolic pathway which converts cysteine to mercaptopyruvate via a PLP-dependent cysteine aminotransferase and subsequently, to mercaptopyruvate sulfur transferase-bound persulfide from which H(2)S can be liberated.

Pre-steady-state kinetic analysis of enzyme-monitored turnover during cystathionine β-synthase-catalyzed H(2)S generation.

Cystathionine β-synthase (CBS) catalyzes the first step in the transsulfuration pathway in mammals, i.e., the condensation of serine and homocysteine to produce cystathionine and water.

Investigations of low-frequency vibrational dynamics and ligand binding kinetics of cystathionine beta-synthase.

Vibrational coherence spectroscopy is used to study the low frequency dynamics of the truncated dimer of human cystathionine beta-synthase (CBS). CBS is a pyridoxal-5'-phosphate-dependent heme enzyme with cysteine and histidine axial ligands that catalyzes the condensation of serine and homocysteine to form cystathionine. A strong correlation between the "detuned" coherence spectrum (which probes higher frequencies) and the Raman spectrum is demonstrated, and a rich pattern of modes below 200 cm(-1) is revealed.

Heme regulation of human cystathionine beta-synthase activity: insights from fluorescence and Raman spectroscopy.

Cystathionine beta-synthase (CBS) plays a central role in homocysteine metabolism, and malfunction of the enzyme leads to homocystinuria, a devastating metabolic disease. CBS contains a pyridoxal 5'-phosphate (PLP) cofactor which catalyzes the synthesis of cystathionine from homocysteine and serine. Mammalian forms of the enzyme also contain a heme group, which is not involved in catalysis.

Relative contributions of cystathionine beta-synthase and gamma-cystathionase to H2S biogenesis via alternative trans-sulfuration reactions.

In mammals, the two enzymes in the trans-sulfuration pathway, cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE), are believed to be chiefly responsible for hydrogen sulfide (H2S) biogenesis. In this study, we report a detailed kinetic analysis of the human and yeast CBS-catalyzed reactions that result in H2S generation. CBS from both organisms shows a marked preference for H2S generation by beta-replacement of cysteine by homocysteine.

H2S biogenesis by human cystathionine gamma-lyase leads to the novel sulfur metabolites lanthionine and homolanthionine and is responsive to the grade of hyperhomocysteinemia.

Although there is a growing recognition of the significance of hydrogen sulfide (H(2)S) as a biological signaling molecule involved in vascular and nervous system functions, its biogenesis and regulation are poorly understood. It is widely assumed that desulfhydration of cysteine is the major source of H(2)S in mammals and is catalyzed by the transsulfuration pathway enzymes, cystathionine beta-synthase and cystathionine gamma-lyase (CSE). In this study, we demonstrate that the profligacy of human CSE results in a variety of reactions that generate H(2)S from cysteine and homocysteine.

Modulation of the heme electronic structure and cystathionine beta-synthase activity by second coordination sphere ligands: The role of heme ligand switching in redox regulation.

In humans, cystathionine beta-synthase (CBS) is a hemeprotein, which catalyzes a pyridoxal phosphate (PLP)-dependent condensation reaction. Changes in the heme environment are communicated to the active site, which is approximately 20A away. In this study, we have examined the role of H67 and R266, which are in the second coordination sphere of the heme ligands, H65 and C52, respectively, in modulating the heme's electronic properties and in transmitting information between the heme and active sites.