An important mechanism underlying cochlear hair cell (HC) susceptibility to hypoxia/ischemia is the influx of Ca2+. Two main ATP-dependent mechanisms contribute to maintaining low Ca2+ levels: uptake of Ca2+ into intracellular stores via smooth endoplasmic reticulum calcium ATPase (SERCA) and extrusion of Ca2+ via plasma membrane calcium ATPase (PMCA). The effects of the SERCA inhibitors thapsigargin (10 nM-10 μM) and cyclopiazonic acid (CPA; 10-50 μM) and of the PMCA blockers eosin (1.5-10 μM) and o-vanadate (1-5 mM) on inner and outer hair cells (IHCs/OHCs) were examined in normoxia and ischemia using an in vitro model of the newborn rat cochlea. Exposure of the cultures to ischemia resulted in a significant loss of HCs. Thapsigargin and CPA had no effect. Eosin decreased the numbers of IHCs and OHCs by up to 25 % in normoxia and significantly aggravated the ischemia-induced damage to IHCs at 5 and 10 μM and to OHCs at 10 μM. o-Vanadate had no effect on IHC and OHC counts in normoxia, but aggravated the ischemia-induced HC loss in a dose-dependent manner. The effects of eosin and o-vanadate indicate that PMCA has an important role to play in protecting the HCs from ischemic cell death., N. Amarjargal, B. Mazurek, H. Haupt, N. Andeeva, J. Fuchs, J. Gross., and Obsahuje bibliografii a bibliografické odkazy
Ca2+ has been considered as a necessary ion for alleviation of stress-induced damages in plants. We investigated effects of exogenous Ca2+ on waterlogging-induced damage to pepper and its underlying mechanisms. Pepper seedlings under stress were treated by spraying of 10 mM CaCl2. Applying exogenous Ca2+ increased the biomass of pepper leaves and roots, improved photosynthetic characteristics, membrane permeability, root activity, osmotic substance contents, antioxidant enzyme and alcohol dehydrogenase activities, while it reduced lactate dehydrogenase activity. It maintained hydroxide radical contents and activities of malate dehydrogenase and succinate dehydrogenase relatively high. Our results suggested that applying exogenous Ca2+ could regulate osmotic substance contents, antioxidant system activity, root respiration, and metabolism, and subsequently alleviate waterlogging-induced damages to pepper plants., B. Z. Yang, Z. B. Liu, S. D. Zhou, L. J. Ou, X. Z. Dai, Y. Q. Ma, Z. Q. Zhang, W. C. Chen, X. F. Li, C. L. Liang, S. Yang, X. X. Zou., and Obsahuje bibliografii
Leptin is a hormone primarily secreted by adipocytes and participating in the regulation of food intake and energy expenditure. Its blood levels usually correlate with adiposity. The secretion of this hormone is affected, among others, by food consumption, insulin, fasting and cold exposure. Regulation of leptin secretion depends on many intracellular events. It is known that the activation of mTOR (the mamma lian target of rapamycin) as well as increase in ATP and malonyl-CoA content in adipocytes enhance secretion of leptin. The rise in intracellular cAMP and fatty acids is thought to evoke the opposite effect. Moreover, the undisturbed action of endogenous adenosine in adipocytes and the proper intracellular Ca2+ concentration in these cells were also found to have an important function in leptin release. The role of mTOR, ATP, cAMP, fatty acids, malonyl-CoA, adenosine and Ca2+ in the regulation of leptin secretion from adipocytes is discussed., T. Szkudelski., and Obsahuje bibliografii a bibliografické odkazy
The role of [Ca2 + ]j and cAMP in transduction of the melatonin inhibitory effect on GnRH-induced LH release from neonatal rat gonadotrophs has been studied, because melatonin inhibits the increase of both intracellular messengers. Treatments increasing Ca2+ influx (S( —) Bay K8644 or KC1) or cAMP concentration (8-bromo-cAMP or 3-isobutyl-l-methylxanthine) potentiated the GnRH-induced LH release and partially diminished the inhibitory effect of melatonin. Combination of the treatments increasing cAMP and calcium concentrations blocked completely the melatonin inhibition of LH release. The combined treatment with 8-bromo-cAMP and S(-) Bay K8644 also blocked the melatonin inhibition of GnRH-induced [Ca2+]j increase in 89% of the gonadotrophs, while any of the treatments alone blocked the melatonin effect in about 25 % of these cells. These observations suggest that a cAMP-dependent pathway is involved in regulation of Ca2+ influx by melatonin and melatonin inhibition of LH release may be mediated by the decrease of both messengers.
Experimental studies have shown a symmetry-to-asymmetry transition of the spike-timing dependent plasticity (STDP) curve exists in the proximal stratum radiatum (SR) dendrite of the hippocampal CA1 pyramidal neuron, which is probably due to the presence of GABAergic inhibition [2, 3, 4]. A recent computational model predicted that symmetry-to-asymmetry transition is strongly dependent on the frequency and conductance value of GABA inhibition and that the largest long term potentiation (LTP) value and the two distinct long-term depression (LTD) tails of the symmetrical STDP curve are centred at +10 ms, +40 ms and -10 ms, respectively [8, 9]. In the present paper, we continue to investigate even further via computer simulations the effects of gamma frequency inhibition and its conductance value to the symmetry-to-asymmetry transition of the STDP profile in the SR dendrite and predict that the transition is even more robust when there is a temporal offset between the onsets of the pre-post excitatory stimulation and the GABAergic inhibition. The largest LTP value and the two distinct LTD tails are inversely proportional to the increase of GABA conductance.
The response properties of feline cold receptors were analyzed under control conditions, during conditions of altered external calcium concentrations and during application of menthol, catecholamines and ouabain. Afferent activity was extracellularly recorded from cold fibres of an isolated preparation of the tongue. Reduced calcium levels (0.5 mM) generally enhanced and elevated calcium levels (5.0 mM) suppressed cold fibre activity. The effects of menthol (105 M) on cold receptors were qualitatively similar to those of reduced calcium. Application of adrenaline and noradrenaline (10-6 M) were predominantly inhibiting. In cold receptors, the mean discharge rate is determined by the frequency of an oscillating receptor process and the probability of each cycle of this process to initiate afferent impulses. All measures mainly affected the probability of impulse generation rather than the oscillation frequency. Application of ouabain (1(F6 M) resulted in excitatory responses, caused by an increase of both probability of impulse generation and frequency of the oscillating receptor process. It is concluded that cold receptor function is based on a specific combination of common neuronal elements rather than on specific sensory processes.
PEP carboxylase (PEPC) in leaves of C4 plants is activated by phosphorylation of enzyme by a PEPC-protein kinase (PEPC-PK). We reevaluated the pattern of PEPC phosphorylation in leaf extracts of Amaranthus hypochondriacus. It was dependent on Ca2+, the optimum concentration of which for stimulation was 10 mM. The extent of stimulation was inhibited by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), a Ca2+ chelator. The inhibition by BAPTA was relieved by the addition of Ca2+ but not by the addition of Mg2+. The stimulation by Ca2+ of PEPC phosphorylation was marginally enhanced by calmodulin (CaM), but not by diacylglycerol (DAG). Phosphorylation was strongly restricted by Ca2+ or Ca2+-CaM-dependent protein kinase inhibitors. Thus phosphorylation of PEPC is Ca2+-dependent in leaves of A. hypochondriacus and a calcium-dependent protein kinase (CDPK) may modulate PEPC-PK and subsequently the phosphorylation status of PEPC. and K. Parvathi ... [et al.].
Dipeptidyl peptidase-IV (DPP-IV, CD26) is a serine protease almost ubiquitously expressed on cell surface and present in body fluids. DPP-IV has been suggested to proteolytically modify a number of biologically active peptides including substance P (SP) and the chemokine stro mal cell derived factor-1α (SDF-1α, CXCL12). SP and SDF-1α have been implicated in the regulation of multiple biological processes and also induce responses that may be relevant for glioma progression. Both SP and SDF-1α are signaling through cell surface receptors and use intracellular calcium as a second messenger. The effect of DPP-IV on intracellular calcium mobilization mediated by SP and SDF- α was monitored in suspension of wild type U373 and DPP-IV transfected U373DPPIV glioma cells using indicator FURA-2. Nanomolar concentrations of SP triggered a transient dose dependent increase in intracellular calcium rendering the cells refractory to repeated stimulation, while SDF-1α had no measurable effect. SP signaling in DPP-IV overexpressing U373DPPIV cells was not substantially different from that in wild type cells. However, preincubation of SP with the DPP-IV overexpressing cells lead to the loss of its signaling potential, which could be prevented with DPP-IV inhibitors. Taken together, DPP-IV may proteolytically inactivate local mediators involved in gliomagenesis., P. Bušek, J, Stremeňová, E. Křepela, A. Šedo., and Obsahuje bibliografii a bibliografické odkazy
Glutamate is a well-characterized excitatory neurotransmitter in the central nervous system (CNS). Recently, glutamate receptors (GluRs) were also found in peripheral tissues, including the heart. However, the function of GluRs in peripheral organs remains poorly understood. In the present study, we found that N-methyl-D-aspartate (NMDA) could increase intracellular calcium ([Ca2+]i) level in a dose-dependent manner in cultured neonatal rat cardiomyocytes. NMDA at 10-4 M increased the levels of reactive oxygen species (ROS), cytosolic cytochrome c (cyto c), and 17-kDa caspase-3, but depolarized mitochondrial membrane potential, leading to cardiomyocyte apoptosis. In addition, NMDA treatment induced an increase in ba x mRNA but a decrease in bcl-2 mRNA expression in the cardiomyocytes. The above effects of NMDA were bloc ked by the NMDA receptor antagonist (+)-5-methyl- 10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801), and by ROS scavengers glutathione (GSH) and N-acetylcystein (NAC). These results suggest that stimulation of NMDA receptor in the cardiomyocyte may lead to apoptosis via a Ca2+, ROS, and caspase-3 mediated pathway. These findings suggest that NMDA receptor may play an important role in myocardial pathogenesis., X. Gao, X. Xu, J. Pang, C. Zhang, J. M. Ding, X. Peng, Y. Liu, J.-M. Cao., and Obsahuje bibliografii a bibliografické odkazy
Orexins (orexin A and B) are initially known to be a hypothalamic peptide critical for feeding and normal wakefulness. In addition, emerging evidence from behavioral tests suggests that orexins are also involved in the regulation of nociceptive processing, suggesting a novel potential therapeutic approach for pain treatment. Both spinal and supraspinal mechanisms appear to contribute to the role of orexin in nociception. In the spinal cord, dorsal root ganglion (DRG) neurons are primary afferent neurons that transmit peripheral stimuli to the pain-processing areas. Morphological results show that both orexin A and orexin-1 receptor are distributed in DRG neurons. Moreover, by using whole-cell patch-clamp recordings and calcium imaging measurements we found that orexin A induced excitability and intracellular calcium concentration elevation in the isolated rat DRG neurons, which was mainly dependent on the activation of spinal orexin-1 receptor. Based on these findings, we propose a hypothesis that the direct effect of orexin A on DRG neurons would represent a possible mechanism for the orexinergic modulation of spinal nociceptive transmission., J.-A. Yan, L. Ge, W. Huang, B. Song, X.-W. Chen, Z.-P. Yu., and Obsahuje bibliografii a bibliografické odkazy