Search results for "Intracellular"

Inhibition of Delta-like 4 mediated signaling induces abortion in mice due to deregulation of decidual angiogenesis.

2013

Objective: To explore whether the Dll4/Notch1 pathway plays a key role in regulating the vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) driven decidual angiogenesis and related pregnancy through induction of a tip/stalk phenotype. Methods: Progesterone-replaced ovariectomized pregnant mice received a single injection of YW152F (Dll4 blocking antibody, BAb) or placebo at embryonic day (E) 4.5. Animals were sacrificed at different time points; blood and uterus were collected for further analysis. Number of embryos and implantation site, uteri weight, and serum progesterone levels were assessed. Alterations in the tip/stalk phenotype were determined by quantitative immunofl…

Decidual endothelial cells express surface-bound C1q as a molecular bridge between endovascular trophoblast and decidual endothelium.

2008

This study was prompted by the observation that decidual endothelial cells (DECs), unlike endothelial cells (ECs) of blood vessels in normal skin, kidney glomeruli and brain, express surface-bound C1q in physiologic pregnancy. This finding was unexpected, because deposits of C1q are usually observed in pathologic conditions and are associated with complement activation. In the case of DECs, we failed to detect immunoglobulins and C4 co-localized with C1q on the cell surface. Surprisingly, DECs expressed mRNA for the three chains of C1q and secreted detectable level of this component in serum-free medium. The ability to synthesize C1q is acquired by DECs during pregnancy and is not shared by…

Antiapoptotic effect of calcitonin gene-related peptide on oxidative stress-induced injury in H9c2 cardiomyocytes via the RAMP1/CRLR complex.

2005

Calcitonin gene-related peptide (CGRP) plays an important role in the mediation of protective effects observed in situations such as ischemic preconditioning in rat hearts. In this study, we investigated in H9c2 rat cardiomyoblasts if the protective effect of CGRP could be linked to an inhibitory effect on the apoptotic pathway. We also determined the specificity of observed effects by treatment with adrenomedullin (ADM) in stress conditions generated by 100 microM hydrogen peroxide. Using MTT assays, we demonstrate that a pretreatment with CGRP decreases by half the loss of cell viability induced by H(2)O(2). CGRP inhibits phosphatidylserine externalization, caspase 3 activation and DNA fr…

Adaptation of neuronal cells to chronic oxidative stress is associated with altered cholesterol and sphingolipid homeostasis and lysosomal function

2009

Chronic oxidative stress has been causally linked to several neurodegenerative disorders. As sensitivity for oxidative stress greatly differs between brain regions and neuronal cell types, specific cellular mechanisms of adaptation to chronic oxidative stress should exist. Our objective was to identify molecular mechanisms of adaptation of neuronal cells after applying chronic sublethal oxidative stress. We demonstrate that cells resistant to oxidative stress exhibit altered cholesterol and sphingomyelin metabolisms. Stress-resistant cells showed reduced levels of molecules involved in cholesterol trafficking and intracellular accumulation of cholesterol, cholesterol precursors, and metabol…

Role of IP3 Receptors in Shaping the Carotid Chemoreceptor Response to Hypoxia But Not to Hypercapnia in the Rat Carotid Body: An Evidence Review

2020

This article addresses the disparity in the transduction pathways for hypoxic and hypercapnic stimuli in carotid body glomus cells. We investigated and reviewed the experimental evidence showing that the response to hypoxia, but not to hypercapnia, is mediated by 1,4,5-inositol triphosphate receptors (IP3R/s) regulating the intracellular calcium content [Ca2+]c in glomus cells. The rationale was based on the past observations that inhibition of oxidative phosphorylation leads to the explicit inhibition of the hypoxic chemoreflex. [Ca2+]c changes were measured using cellular Ca2+-sensitive fluorescent probes, and carotid sinus nerve (CSN) sensory discharge was recorded with bipolar electrode…

Intestinal filtration as a consequence of increased mucosal hydraulic permeability

1980

Two mechanisms have been proposed to explain the secretory action of laxative compounds in the intestine: 1. increase of the intracellular amount of cyclic adenosine monophosphate due to stimulation of the adenylate cyclase system and 2. inhibition of intestinal transfer processes, in particular the Na,K-ATPase activated sodium absorption. In a set of in vivo and in vitro experiments in rat colon it could be demonstrated that dihydroxy bile acids (deoxycholate) and diphenolic laxatives (oxyphenisatin) enhance the hydraulic permeability of the mucosal tissue. The permeability changes take place--and there is good experimental evidence--at the zonulae occludentes which bind the epithelial cel…

Magnesium metabolism in type 2 diabetes mellitus, metabolic syndrome and insulin resistance

2007

Type 2 diabetes is characterized by cellular and extracellular Mg depletion. Epidemiologic studies showed a high prevalence of hypomagnesaemia and lower intracellular Mg concentrations in diabetic subjects. Insulin and glucose are important regulators of Mg metabolism. Intracellular Mg plays a key role in regulating insulin action, insulin-mediated-glucose uptake and vascular tone. Reduced intracellular Mg concentrations result in a defective tyrosine-kinase activity, post-receptorial impairment in insulin action, and worsening of insulin resistance in diabetic patients. Mg deficit has been proposed as a possible underlying common mechanism of the "insulin resistance" of different metabolic…

Efavirenz induces alterations in lipid metabolism through AMPK activation

2008

Summary of results EFV produced an immediate reduction of mitochondrialfunction, evident by the significant and dose-dependentinhibition of mitochondrial O2 consumption and thedecrease of intracellular ATP and Δψm. This metabolicstress promoted the activation of AMPK, triggering severalof its signalling pathways, as EFV induced an increment inCD36 mRNA expression and in intracellular lipid content,which could have been a result of the formation of lipiddroplets. This intracellular lipid increase was not presentin cells treated with Compound C, which points to a keyrole for AMPK in these mechanisms. Conclusion Given that EFV treatment is usually prolonged, thesemechanisms may effect the gene…

Influence of different CyA formulations and calcium channel blocker phenyhidine regimens on intracellular (erythrocyte) calcium levels after kidney t…

1997

Inhibition of intracellular Ca2+ release by a Rho-kinase inhibitor for the treatment of ischemic damage in primary cultured rat hippocampal neurons.

2008

The effects of hydroxy fasudil, a specific Rho-kinase inhibitor, on behavior and brain neuronal activity in animal studies have been described previously. However, whether a Rho-kinase inhibitor can directly protect neurons against ischemic damage and the molecular mechanisms underlying these effects are poorly understood. The present work was designed to investigate the effect of hydroxy fasudil against oxygen-glucose deprivation (OGD) induced acute neuronal injury and the underlying mechanisms in vitro. Pretreatment with hydroxy fasudil at 5 and 10 microM could concentration-dependently improve cell viability and decrease Lactate dehydrogenase (LDH) level in extracellular solution of neur…