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Phosphate Production (phosphate + production)
Selected AbstractsImpaired oxygen kinetics in beta-thalassaemia major patientsACTA PHYSIOLOGICA, Issue 3 2009I. Vasileiadis Abstract Aim:, Beta-thalassaemia major (TM) affects oxygen flow and utilization and reduces patients' exercise capacity. The aim of this study was to assess phase I and phase II oxygen kinetics during submaximal exercise test in thalassaemics and make possible considerations about the pathophysiology of the energy-producing mechanisms and their expected exercise limitation. Methods:, Twelve TM patients with no clinical evidence of cardiac or respiratory disease and 10 healthy subjects performed incremental, symptom-limited cardiopulmonary exercise testing (CPET) and submaximal, constant workload CPET. Oxygen uptake (Vo2), carbon dioxide output and ventilation were measured breath-by-breath. Results:, Peak Vo2 was reduced in TM patients (22.3 ± 7.4 vs. 28.8 ± 4.8 mL kg,1 min,1, P < 0.05) as was anaerobic threshold (13.1 ± 2.7 vs. 17.4 ± 2.6 mL kg,1 min,1, P = 0.002). There was no difference in oxygen cost of work at peak exercise (11.7 ± 1.9 vs. 12.6 ± 1.9 mL min,1 W,1 for patients and controls respectively, P = ns). Phase I duration was similar in TM patients and controls (24.6 ± 7.3 vs. 23.3 ± 6.6 s respectively, P = ns) whereas phase II time constant in patients was significantly prolonged (42.8 ± 12.0 vs. 32.0 ± 9.8 s, P < 0.05). Conclusion:, TM patients present prolonged phase II on-transient oxygen kinetics during submaximal, constant workload exercise, compared with healthy controls, possibly suggesting a slower rate of high energy phosphate production and utilization and reduced oxidative capacity of myocytes; the latter could also account for their significantly limited exercise tolerance. [source] Cyclooxygenase-2 Expression and Prostaglandin E2 Production in Response to Acidic pH Through OGR1 in a Human Osteoblastic Cell Line,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2008Hideaki Tomura Abstract Acidosis has been shown to induce depletion of bone calcium from the body. This calcium release process is thought to be partially cell mediated. In an organ culture of bone, acidic pH has been shown to induce cyclooxygenase-2 (COX-2) induction and prostaglandin E2 (PGE2) production, resulting in stimulation of bone calcium release. However, the molecular mechanisms whereby osteoblasts sense acidic circumstances and thereby induce COX-2 induction and PGE2 production remain unknown. In this study, we used a human osteoblastic cell line (NHOst) to characterize cellular activities, including inositol phosphate production, intracellular Ca2+ concentration ([Ca2+]i), PGE2 production, and COX-2 mRNA and protein expression, in response to extracellular acidification. Small interfering RNA (siRNA) specific to the OGR1 receptor and specific inhibitors for intracellular signaling pathways were used to characterize acidification-induced cellular activities. We found that extracellular acidic pH induced a transient increase in [Ca2+]i and inositol phosphate production in the cells. Acidification also induced COX-2 induction, resulting in PGE2 production. These proton-induced actions were markedly inhibited by siRNA targeted for the OGR1 receptor and the inhibitors for Gq/11 protein, phospholipase C, and protein kinase C. We conclude that the OGR1/Gq/11/phospholipase C/protein kinase C pathway regulates osteoblastic COX-2 induction and subsequent PGE2 production in response to acidic circumstances. [source] Transmembrane signaling through phospholipase C-, in the developing human prefrontal cortexJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2006Iñigo Ruiz de Azúa Abstract To investigate changes in muscarinic receptor-stimulated phospholipase C-, (PLC-,) activity during brain development, we examined the functional coupling of each of the three major protein components of the phosphoinositide system (M1, M3, and M5 muscarinic receptor subtypes; Gq/11 proteins; PLC-,1,4 isoforms) in membrane preparations from post-mortem human prefrontal cerebral cortex collected at several stages of prenatal and postnatal development. In human prenatal brain membranes, PLC was found to be present and could be activated by calcium, but the ability of guanosine-5,-o-3 thiotriphosphate (GTP,S) or carbachol (in the presence of GTP,S) to modulate prenatal PLC-, was significantly weaker than that associated with postnatal PLC-,. Western blot analysis revealed that the levels of G,q/11 did not change significantly during development. In contrast, dramatically higher levels of expression of PLC-,1,4 isoforms and of M1, M3, and M5 muscarinic receptors were detected in the child vs. the fetal brain, a finding that might underlie the observed increased activity of PLC. Thus, inositol phosphate production may be more efficiently regulated by altering the amount of effectors (PLC-,1,4) and receptors (M1,3,5 subtypes) than by altering the level of G,q/11 subunits. These results demonstrate that different PLC isoforms are expressed in the prefrontal cortex of the developing human brain in an age-specific manner, suggesting specific roles not only in synaptic transmission but also in the differentiation and maturation of neurons in the developing brain. © 2006 Wiley-Liss, Inc. [source] ,1 -Adrenoceptor effects mediated by protein kinase C , in human cultured prostatic stromal cellsBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2003A Preston We have investigated the effects of ,1 -adrenoceptor stimulation upon contractility, Ca2+ influx, inositol phosphate production, and protein kinase C (PKC) translocation in human cultured prostatic stromal cells (HCPSC). The ,1 -adrenoceptor selective agonist phenylephrine elicited contractile responses of HCPSC, i.e. a maximal cell shortening of 45±6% of initial cell length, with an EC50 of 1.6±0.1 ,M. The ,1 -adrenoceptor selective antagonists prazosin (1 ,M) and terazosin (1 ,M) both blocked contractions to phenylephrine (10 ,M). The L-type calcium channel blocker nifedipine (10 ,M), and the PKC inhibitors Gö 6976 (1 ,M) and bisindolylmaleimide (1 ,M) also inhibited phenylephrine-induced contractions. Phenylephrine caused a concentration dependent increase in inositol phosphate production (EC50 119±67 nM). This response was blocked by terazosin (1 ,M). Phenylephrine caused the translocation of the PKC , isoform, but not the ,, ,, ,, , or , isoforms, from the cytosolic to the particulate fraction of HCPSC, with an EC50 of 5.7±0.5 ,M. In FURA-2AM (5 ,M) loaded cells, phenylephrine elicited concentration dependent increases in [Ca2+]i, with an EC50 of 3.9±0.4 ,M. The response to phenylephrine (10 ,M) was blocked by prazosin (1 ,M), bisindolymaleimide (1 ,M), and nifedipine (10 ,M). In conclusion, this study has shown that HCPSC express functional ,1 -adrenoceptors, and that the intracellular pathways responsible for contractility may be largely dependent upon protein kinase C activation and subsequent opening of L-type calcium channels. British Journal of Pharmacology (2003) 138, 218,224. doi:10.1038/sj.bjp.0705021 [source] | |||||||||||||