Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PGE2 and PGA2 incubated for 30 min at 25 degrees C with microsomal membranes isolated from Walker-256 tumour, in the presence of 50 microM indomethacin increase the lipid fluidity estimated by steady-state fluorescence anisotropy [(r0/r)-1]-1, using 1,6-diphenyl-1,3,5-hexatriene (DPH) as probe. The microsomal preparations of Walker-256 tumour contained calcium-stimulated and magnesium-dependent ATPase as well as calmoduling-dependent guanylate cyclese activities. A considerable decrease (approx. 65%) in the activity of the Ca2+-stimulated ATPase was observed when preparations were treated with 10 microM PGE2 and PGA2. A dramatic gradual decrease of the calmodulin-dependent guanylate cyclase activity was also observed at different concentrations of PGE2 and PGA2 (0.25-10 microM). The ATP-dependent uptake of calcium was reduced by approximately 60% in microsomal membranes treated with PGE2 and PGA2. The allosteric properties of Ca2+-stimulated ATPase by Na+, and of guanylate cyclase by Mn.GTP (as reflected by changes in the Hill coefficients, h) were modulated by PGE2 and PGA2. The apparent cooperativity of the Ca2+-ATPase (h + 1.73 +/- 0.21) in control membranes was abolished (h + 1.1 +/- 0.11 and h = 0.9 +/- 0.09) in membranes treated by PGE2 and PGA2 (10 microM), while the allosteric stimulation of guanylate cyclase by Mn.GTP was reduced from h = 2.78 +/- 0.24 in control membranes to h = 1.92 +/- 0.16 and h = 1.73 +/- 0.15 in membranes treated by PGE2 and PGA2 (10 microM), respectively, suggesting that the physical state of Ca2+-stimulated ATPase and guanylate cyclase lipid microenvironments changed from a gel phase to a liquid-crystalline phase. In conclusion, it is suggested that PGE2 and PGA2 promote a phase separation in Walker-256 tumour microsomal membranes. This may be relevant to the Ca2+-calmodulin system and tumour growth inhibition.
 ...
PMID:PGE2 and PGA2 affect the allosteric properties and the activities of calmodulin-dependent guanylate cyclase and Ca2+-stimulated ATPase of Walker-256 tumour microsomal membranes. 256 56

Based on our previous findings on the modifying effect of calmodulin (CaM) on the physiochemical properties of biomembrane, we have investigated the possible relationship between intracellular CaM content and endoplasmic reticulum (ER) membrane fluidity and function during liver regeneration. The degree of ER membrane fluidity was estimated by fluorescence polarization analysis with the 1,6-diphenyl-1,3,5-hexatriene probe. Microsomal guanylate cyclase (GC) was used as a functional parameter. The kinetics of the increase in the ER membrane fluidity during liver regeneration was strictly parallel to the CaM surge and was matched by an increase in GC activity. The stimulative effect of splenectomy on liver regeneration and its inhibition by Walker-256 tumor, inferred from the corresponding alterations of CaM levels, were mirrored by the modulation in GC activity. The fluidizing effect of CaM on ER membrane was concluded from the drop in thermotropic transition temperature from 28.3 +/- 1.6 degrees C in control membranes to 17.8 +/- 1.1 degrees C membranes from regenerating livers and to 19.8 +/- 1.2 degrees C in control membranes treated with CaM. Arrhenius plots of GC activity exhibited a transition temperature of 25.5 +/- 1.25 degrees C in controls, which shifted to 20.5 +/- 0.9 degrees C in ER membranes from regenerating livers and to 21.7 +/- 1.1 degrees C in control membranes treated with CaM. The Hill coefficient for the allosteric activation of the GC by Mn.GTP decreased from 1.49 +/- 0.16 in controls to 0.93 +/- 0.085 in membranes from regenerating cells and to 0.86 +/- 0.073 in CaM-treated membranes. Both effects of CaM were consistent with a fluidity increase in the enzyme's lipid microenvironment. The results of the present study suggest that an early key event in liver regeneration may be the CaM-induced modulation of ER membrane fluidity and function.
 ...
PMID:Calmodulin-related changes in microsomal membrane fluidity during liver regeneration. 907 62