Biochemical Aspects (biochemical + aspect)

Distribution by Scientific Domains
Chemistry50%

Selected Abstracts

EFFECT OF THE PHOSPHODIESTERASE 5 INHIBITORS SILDENAFIL, TADALAFIL AND VARDENAFIL ON RAT ANOCOCCYGEUS MUSCLE: FUNCTIONAL AND BIOCHEMICAL ASPECTS

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2009
Haroldo A Toque
SUMMARY 1The anococcygeus muscle is part of the erectile machinery in male rodents. Phosphodiesterase (PDE) 5 inhibitors enhance and prolong the effects of cGMP, which has a key role in penile erection. The aim of the present study was to provide a functional and biochemical comparison of the three PDE5 inhibitors, namely sildenafil, tadalafil and vardenafil, in the rat anococcygeus muscle. 2Muscle strips were mounted in 4 mL organ baths and isometric force recorded. Levels of cGMP were measured using an enzyme immunoassay kit. Western blots were used to determine PDE5 protein expression. 3The PDE5 inhibitors concentration-dependently relaxed carbachol-precontracted anococcygeus muscle; however, vardenafil was more potent (pEC50 = 8.11 ± 0.05) than sildenafil (7.72 ± 0.06) or tadalafil (7.69 ± 0.05). Addition of NG -nitro- l -arginine methyl ester (100 µmol/L) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 µmol/L) to the organ baths caused significant rightward shifts in concentration,response curves for all PDE5 inhibitors. 4Sildenafil, tadalafil and vardenafil (all at 0.1 µmol/L) caused leftward shifts in the glyceryl trinitrate (GTN) concentration-response curves (by 4.0-, 3.7- and 5.5-fold, respectively). In addition, all three PDE5 inhibitors significantly potentiated relaxation responses to both GTN (0.01,10 µmol/L) and electrical field stimulation (EFS; 1,32 Hz), with vardenafil having more pronounced effects. 5All three PDE5 inhibitors reduced EFS-evoked contractions in a concentration-dependent manner over the concentration range 0.001,1 µmol/L. There were no significant differences between the effects of the three PDE5 inhibitors. 6Vardenafil (0.01,0.1 µmol/L) was more potent in preventing cGMP degradation in vitro than sildenafil (0.01,0.1 µmol/L) and tadalafil (0.01,0.1 µmol/L). 7Under control conditions, the expression of PDE5 was higher in the anococcygeus muscle than in the corpus cavernosum. 8In conclusion, PDE5 inhibitors enhance exogenous and endogenous nitric oxide-mediated relaxation in the rat anococcygeus muscle. The potency of vardenafil was greater than that of either sildenafil or tadalafil. [source]

Biochemical aspects in two minimally processed lettuces upon storage

INTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 2 2007
Silvia Tavarini
Summary The browning process was studied in two cultivars of minimally processed lettuce (Lactuca sativa var. capitata cv. Verpia and Lactuca sativa var. acephala cv. Lollo Rossa). The analyses were carried out upon storage at 4 °C in the dark. The first interesting result was the resistance to browning of excised leaves of Lollo Rossa, that did not present the typical symptoms of browning. Another important characteristic of Lollo Rossa lettuce was the higher antioxidant ability before storage. The results of biochemical characteristics obtained in this experiment did not show clear evidence supporting the biochemical model of tissue browning involving the sequential synthesis of phenolics and quinones that are regulated, respectively, by phenyl alanine ammonia-lyase, polyphenol oxidase and/or peroxidase. [source]

Biochemical aspects of the neuroprotective mechanism of PTEN-induced kinase-1 (PINK1)

JOURNAL OF NEUROCHEMISTRY, Issue 1 2008
Ryan D. Mills
Abstract Mutations in PTEN-induced kinase 1 (PINK1) gene cause PARK6 familial Parkinsonism. To decipher the role of PINK1 in pathogenesis of Parkinson's disease (PD), researchers need to identify protein substrates of PINK1 kinase activity that govern neuronal survival, and establish whether aberrant regulation and inactivation of PINK1 contribute to both familial Parkinsonism and idiopathic PD. These studies should take into account the several unique structural and functional features of PINK1. First PINK1 is a rare example of a protein kinase with a predicted mitochondrial-targeting sequence and a possible resident mitochondrial function. Second, bioinformatic analysis reveals unique insert regions within the kinase domain that are potentially involved in regulation of kinase activity, substrate selectivity and stability of PINK1. Third, the C-terminal region contains functional motifs governing kinase activity and substrate selectivity. Fourth, accumulating evidence suggests that PINK1 interacts with other signaling proteins implicated in PD pathogenesis and mitochondrial dysfunction. The most prominent examples are the E3 ubiquitin ligase Parkin, the mitochondrial protease high temperature requirement serine protease 2 and the mitochondrial chaperone tumor necrosis factor receptor-associated protein 1. How PINK1 may regulate these proteins to maintain neuronal survival is unclear. This review describes the unique structural features of PINK1 and their possible roles in governing mitochondrial import, processing, kinase activity, substrate selectivity and stability of PINK1. Based upon the findings of previous studies of PINK1 function in cell lines and animal models, we propose a model on the neuroprotective mechanism of PINK1. This model may serve as a conceptual framework for future investigation into the molecular basis of PD pathogenesis. [source]

Structural Diversity of PDZ,Lipid Interactions

CHEMBIOCHEM, Issue 4 2010
Rodrigo Gallardo
Abstract PDZ domains are globular protein modules that are over-and-above appreciated for their interaction with short peptide motifs found in the cytosolic tail of membrane receptors, channels, and adhesion molecules. These domains predominate in scaffold molecules that control the assembly and the location of large signaling complexes. Studies have now emerged showing that PDZ domains can also interact with membrane lipids, and in particular with phosphoinositides. Phosphoinositides control various aspects of cell signaling, vesicular trafficking, and cytoskeleton remodeling. When investigated, lipid binding appears to be extremely relevant for PDZ protein functionality. Studies point to more than one mechanism for PDZ domains to associate with lipids. Few studies have been focused on the structural basis of PDZ,phosphoinositide interactions, and the biological consequences of such interactions. Using the current knowledge on syntenin-1, syntenin-2, PTP-Bas, PAR-3 and PICK1, we recapitulate our understanding of the structural and biochemical aspects of PDZ,lipid interactions and the consequences for peptide interactions. [source]