Activation of Cx43 Hemichannels Induces the Generation of Ca Oscillations in White Adipocytes and Stimulates Lipolysis.

The aim of the study was to investigate the mechanisms of Ca oscillation generation upon activation of connexin-43 and regulation of the lipolysis/lipogenesis balance in white adipocytes through vesicular ATP release. With fluorescence microscopy it was revealed that a decrease in the concentration of extracellular calcium ([Ca]) results in two types of Ca responses in white adipocytes: Ca oscillations and transient Ca signals. It was found that activation of the connexin half-channels is involved in the generation of Ca oscillations, since the blockers of the connexin hemichannels-carbenoxolone, octanol, proadifen and Gap26-as well as Cx43 gene knockdown led to complete suppression of these signals.

Deregulation of Ca-Signaling Systems in White Adipocytes, Manifested as the Loss of Rhythmic Activity, Underlies the Development of Multiple Hormonal Resistance at Obesity and Type 2 Diabetes.

Various types of cells demonstrate ubiquitous rhythmicity registered as simple and complex Ca-oscillations, spikes, waves, and triggering phenomena mediated by G-protein and tyrosine kinase coupled receptors. Phospholipase C/IP-receptors (PLC/IPR) and endothelial NO-synthase/Ryanodine receptors (NOS/RyR)-dependent Ca signaling systems, organized as multivariate positive feedback generators (PLC-G and NOS-G), underlie this rhythmicity. Loss of rhythmicity at obesity may indicate deregulation of these signaling systems.

Interleukin-10 restores glutamate receptor-mediated Ca-signaling in brain circuits under loss of transcription factor.

Objective: This study aimed to investigate the connection between the mutation of the transcription factor and impaired Ca-signaling, which reflects changes in neurotransmission in the cerebral cortex .

Methods: We used mixed neuroglial cortical cell cultures derived from mutant mice. The cells were loaded with a fluorescent ratiometric calcium-sensitive probe Fura-2 AM and epileptiform activity was modeled by excluding magnesium ions from the external media or adding a GABA(A) receptor antagonist, bicuculline.

BDNF Overexpression Enhances the Preconditioning Effect of Brief Episodes of Hypoxia, Promoting Survival of GABAergic Neurons.

Hypoxia causes depression of synaptic plasticity, hyperexcitation of neuronal networks, and the death of specific populations of neurons. However, brief episodes of hypoxia can promote the adaptation of cells. Hypoxic preconditioning is well manifested in glutamatergic neurons, while this adaptive mechanism is virtually suppressed in GABAergic neurons.

The selective BDNF overexpression in neurons protects neuroglial networks against OGD and glutamate-induced excitotoxicity.

Cerebral ischemia is accompanied by damage and death of a significant number of neurons due to glutamate excitotoxicity with subsequent a global increase of cytosolic Ca concentration ([Ca]). This study aimed to investigate the neuroprotective action of BDNF overexpression in hippocampal neurons against injury under ischemia-like conditions (oxygen and glucose deprivation) and glutamate-induced excitotoxicity (GluTox). The overexpression of BDNF was reached by the transduction of cell cultures with the adeno-associated (AAV)-Syn-BDNF-EGFP virus construct.

Taxifolin protects neurons against ischemic injury in vitro via the activation of antioxidant systems and signal transduction pathways of GABAergic neurons.

Cerebral blood flow disturbances lead to the massive death of brain cells. The death of >80% of cells is observed in hippocampal cell cultures after 40 min of oxygen and glucose deprivation (ischemia-like conditions, OGD). However, there are some populations of GABAergic neurons which are characterized by increased vulnerability to oxygen-glucose deprivation conditions.

Mutation in the Sip1 transcription factor leads to a disturbance of the preconditioning of AMPA receptors by episodes of hypoxia in neurons of the cerebral cortex due to changes in their activity and subunit composition. The protective effects of interleukin-10.

The Sip1 mutation plays the main role in pathogenesis of the Mowat-Wilson syndrome, which is characterized by the pronounced epileptic symptoms. Cortical neurons of homozygous mice with Sip1 mutation are resistant to AMPA receptor activators. Disturbances of the excitatory signaling components are also observed on such a phenomenon of neuroplasticity as hypoxic preconditioning.

Sip-1 mutations cause disturbances in the activity of NMDA- and AMPA-, but not kainate receptors of neurons in the cerebral cortex.

Smad-interacting protein-1 (Sip1) [Zinc finger homeobox (Zfhx1b), Zeb2] is a transcription factor implicated in the genesis of Mowat-Wilson syndrome (MWS) in humans. MWS is a rare genetic autosomal dominant disease caused by a mutation in the Sip1 gene (aka Zeb2 or Zfhx1b) mapped to 2q22.3 locus.

Cytokine IL-10, activators of PI3-kinase, agonists of α-2 adrenoreceptor and antioxidants prevent ischemia-induced cell death in rat hippocampal cultures.

In the present work we compared the protective effect of anti-inflammatory cytokine IL-10 with the action of a PI3-kinase selective activator 740 Y-P, selective agonists of alpha-2 adrenoreceptor, guanfacine and UK-14,304, and compounds having antioxidant effect: recombinant human peroxiredoxin 6 and B27, in hippocampal cell culture during OGD (ischemia-like conditions). It has been shown that the response of cells to OGD in the control includes two phases. The first phase was accompanied by an increase in the frequency of spontaneous synchronous Ca-oscillations (SSCO) in neurons and Ca-pulse in astrocytes.

Angiotensin II activates different calcium signaling pathways in adipocytes.

Angiotensin II (Ang II) is an important mammalian neurohormone involved in reninangiotensin system. Ang II is produced both constitutively and locally by RAS systems, including white fat adipocytes. The influence of Ang II on adipocytes is complex, affecting different systems of signal transduction from early Са(2+) responses to cell proliferation and differentiation, triglyceride accumulation, expression of adipokine-encoding genes and adipokine secretion.

Anti-inflammatory cytokine interleukin-10 increases resistance to brain ischemia through modulation of ischemia-induced intracellular Ca²⁺ response.

It is suggested that anti-inflammatory cytokine interleukin-10 (IL-10) mediates the delayed protective effects through activation of Jak-Stat3, PI3K-Akt and NF-κB signaling pathways. However, our previous experiments have demonstrated that IL-10 is capable to exert the rapid neuroprotective action through modulation of hypoxia-induced intracellular Ca(2+) ([Ca(2+)]i) response. The first purpose of the present study was to evaluate the neuroprotective effects of IL-10 using three models of the ischemic insults in rats: permanent middle cerebral artery occlusion, ischemia in acute hippocampal slices in vitro and ischemia in cultured hippocampal cells in vitro.

Short-term episodes of hypoxia induce posthypoxic hyperexcitability and selective death of GABAergic hippocampal neurons.

We have previously developed a rat hippocampal neuronal cell model for the registration of the preconditioning effect and posthypoxic hyperexcitability (Turovskaya et al., 2011). Repeated episodes of short-term hypoxia are reported to suppress the amplitude of Ca(2+) response to NMDA in majority of neurons, reflecting the effect of preconditioning in the culture.

Acetylcholine promotes Ca2+ and NO-oscillations in adipocytes implicating Ca2+→NO→cGMP→cADP-ribose→Ca2+ positive feedback loop--modulatory effects of norepinephrine and atrial natriuretic peptide.

Purpose: This study investigated possible mechanisms of autoregulation of Ca(2+) signalling pathways in adipocytes responsible for Ca(2+) and NO oscillations and switching phenomena promoted by acetylcholine (ACh), norepinephrine (NE) and atrial natriuretic peptide (ANP).

Methods: Fluorescent microscopy was used to detect changes in Ca(2+) and NO in cultures of rodent white adipocytes. Agonists and inhibitors were applied to characterize the involvement of various enzymes and Ca(2+)-channels in Ca(2+) signalling pathways.

Interleukin-10 modulates [Ca2+]i response induced by repeated NMDA receptor activation with brief hypoxia through inhibition of InsP(3)-sensitive internal stores in hippocampal neurons.

The goal of this study was to evaluate an effect of interleukin-10 (IL-10) on the Ca(2+) response induced by repeated NMDA receptor activation with brief hypoxia in cultured hippocampal neurons. We focused on the importance of internal Ca(2+) stores in the modulation of this Ca(2+) response by IL-10. To test this, we compared roles of InsP(3)- and ryanodine-sensitive internal stores in the effects of IL-10.

Repeated brief episodes of hypoxia modulate the calcium responses of ionotropic glutamate receptors in hippocampal neurons.

The aim of this study was to evaluate the intracellular cytosolic calcium concentration ([Ca(2+)](i)) changes induced by activation of ionotropic glutamate receptors in cultured hippocampal neurons after repeated brief episodes of hypoxia. To investigate what kinds of ionotropic glutamate receptors are involved we used specific agonists for AMPA- and NMDA-type glutamate receptors. Measurements of [Ca(2+)](i) in cultured hippocampal neurons were made by imaging Fura-2AM loaded hippocampal cells.

Bis(dialkylamide)hydrogen dibromobromate precursors of hypobromite ion in reactions with nerve and blister agent simulants.

Hypobromite ion, BrO(-), is an effective alpha-nucleophile that reacts rapidly with activated phosphorus(V) and sulfonate esters. The parent acid rapidly oxidizes organic sulfides and aryloxide ions. At pH 10-11 BrO(-) and HOBr coexist in water and are potentially useful as decontaminants of chlorosulfide blister agents and the phosphonyl nerve agents.