NOS inhibition synchronizes calcium oscillations in human adipose tissue‐derived mesenchymal stem cells by increasing gap‐junctional coupling

Sauer, Heinrich; Sharifpanah, Fatemeh; M, Hatry; Steffen, Paul; Bartsch, Caroline; Heller, Regine; Padmasekar, Manju; Howaldt, Hans‐Peter; Bein, Gregor; Wartenberg, Maria

doi:10.1002/jcp.22495

Cited by 24 publications

(16 citation statements)

References 39 publications

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“…22 Fluorescence recovery was approximately 14% in control-treated thrombi but reduced to 2% in the presence of 37,43 Gap27, a connexin mimetic peptide (SRPTEKTIFII) designed to target the extracellular loops of Cx37 and Cx43, and the non-isotype selective connexin inhibitors, carbenoxolone (100μM) or 18β-GA (100μM) (Figure 2B). These observations are consistent with previous FRAP studies of gap junctions between adipose tissue-derived mesenchymal stem cells, 30 and provide strong evidence for the involvement of gap junction-mediated intercellular communication between platelets within a thrombus.…”

Section: Resultssupporting

confidence: 91%

Gap Junctions and Connexin Hemichannels Underpin Hemostasis and Thrombosis

et al. 2012

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Background Connexins are a widespread family of membrane proteins that assemble into hexameric hemichannels, also known as connexons. Connexons regulate membrane permeability in individual cells or couple between adjacent cells to form gap junctions and thereby provide a pathway for regulated intercellular communication. We have now examined the role of connexins in platelets, blood cells that circulate in isolation, but upon tissue injury adhere to each other and the vessel wall to prevent blood loss and facilitate wound repair. Methods and Results We report the presence of connexins in platelets, notably connexin37, and that the formation of gap junctions within platelet thrombi is required for the control of clot retraction. Inhibition of connexin function modulated a range of platelet functional responses prior to platelet-platelet contact, and reduced laser induced thrombosis in vivo in mice. Deletion of the Cx37 gene (Gja4) in transgenic mice reduced platelet aggregation, fibrinogen binding, granule secretion and clot retraction indicating an important role for Cx37 hemichannels and gap junctions in platelet thrombus function. Conclusions Together, these data demonstrate that platelet gap junctions and hemichannels underpin the control of haemostasis and thrombosis and represent potential therapeutic targets.

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Section: Resultssupporting

confidence: 91%

Gap Junctions and Connexin Hemichannels Underpin Hemostasis and Thrombosis

et al. 2012

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“…1C, D). This is consistent with data from human bone marrow-and adipose tissue-derived mesenchymal stem cells[38,39].Moreover, the decrease in Ca 2+ oscillation during AFMSC osteoblastic differentiation (Figs.1C, D) is in agreement with previous reports[34,40]. On the other hand, the observed increment in basal [Ca 2+ ]i is in line with the adipocyte differentiation program[41], as an increment in [Ca 2+ ]i upregulates the expression of PPARγ, a nuclear hormone receptor that acts as a critical transcriptional factor in adipocyte differentiation[42].…”

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confidence: 89%

Molecular and Phenotypic Characterization of Human Amniotic Fluid-Derived Cells: A Morphological and Proteomic Approach

Pipino

PierdomenicoLaura

TomoPamela

et al. 2015

Stem Cells and Development

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Mesenchymal Stem Cells derived from Amniotic Fluid (AFMSCs) are multipotent cells of great interest for regenerative medicine. Two predominant cell types, that is, Epithelial-like (E-like) and Fibroblast-like (F-like), have been previously detected in the amniotic fluid (AF). In this study, we examined the AF from 12 donors and observed the prevalence of the E-like phenotype in 5, whereas the F-like morphology was predominant in 7 samples. These phenotypes showed slight differences in membrane markers, with higher CD90 and lower Sox2 and SSEA-4 expression in F-like than in E-like cells; whereas CD326 was expressed only in the E-like phenotype. They did not show any significant differences in osteogenic, adipogenic or chondrogenic differentiation. Proteomic analysis revealed that samples with a predominant E-like phenotype (HC1) showed a different profile than those with a predominant F-like phenotype (HC2). Twenty-five and eighteen protein spots were differentially expressed in HC1 and HC2 classes, respectively. Of these, 17 from HC1 and 4 from HC2 were identified by mass spectrometry. Protein-interaction networks for both phenotypes showed strong interactions between specific AFMSC proteins and molecular chaperones, such as preproteasomes and mature proteasomes, both of which are important for cell cycle regulation and apoptosis. Collectively, our results provide evidence that, regardless of differences in protein profiling, the prevalence of E-like or F-like cells in AF does not affect the differentiation capacity of AFMSC preparations. This may be valuable information with a view to the therapeutic use of AFMSCs.

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“…Our current observations indicate that NADPH oxidase complex is unlikely to be involved in the increase of ROS production induced by moderate electrical stimulation in primary rat skeletal muscle cells. However, in addition to the NADPH oxidase system, DPI can also inhibit the activities of mitochondria, nitric oxide synthase, and of a wide range of flavin‐containing enzymes such as xanthine oxidase, all of which are potential sites for ROS generation (Holland et al, 1973; Ragan and Bloxham, 1977; Rand and Li, 1993; Majander et al, 1994; Li and Trush, 1998; Galkin and Brandt, 2005; Sauer et al, 2011). The concentration of DPI used in the present study (2 µM) is five times lower than that typically reported by others, although we cannot fully guarantee that DPI inhibited the activity of NADPH oxidase only and a contribution of the NADPH oxidase for superoxide production induced by electrical stimulation cannot be fully ruled out.…”

Section: Discussionmentioning

confidence: 99%

Effects of moderate electrical stimulation on reactive species production by primary rat skeletal muscle cells: Cross talk between superoxide and nitric oxide production

Lambertucci

Silveira

Hirabara

et al. 2012

Journal Cellular Physiology

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The effects of a moderate electrical stimulation on superoxide and nitric oxide production by primary cultured skeletal muscle cells were evaluated. The involvement of the main sites of these reactive species production and the relationship between superoxide and nitric oxide production were also examined. Production of superoxide was evaluated by cytochrome c reduction and dihydroethidium oxidation assays. Electrical stimulation increased superoxide production after 1 h incubation. A xanthine oxidase inhibitor caused a partial decrease of superoxide generation and a significant amount of mitochondria-derived superoxide was also observed. Nitric oxide production was assessed by nitrite measurement and by using 4,5-diaminofluorescein diacetate (DAF-2-DA) assay. Using both methods an increased production of nitric oxide was obtained after electrical stimulation, which was also able to induce an increase of iNOS content and NF-κB activation. The participation of superoxide in nitric oxide production was investigated by incubating cells with DAF-2-DA in the presence or absence of electrical stimulation, a superoxide generator system (xanthine-xanthine oxidase), a mixture of NOS inhibitors and SOD-PEG. Our data show that the induction of muscle contraction by a moderate electrical stimulation protocol led to an increased nitric oxide production that can be controlled by superoxide generation. The cross talk between these reactive species likely plays a role in exercise-induced maintenance and adaptation by regulating muscular glucose metabolism, force of contraction, fatigue, and antioxidant systems activities.

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NOS inhibition synchronizes calcium oscillations in human adipose tissue‐derived mesenchymal stem cells by increasing gap‐junctional coupling

Cited by 24 publications

References 39 publications

Gap Junctions and Connexin Hemichannels Underpin Hemostasis and Thrombosis

Gap Junctions and Connexin Hemichannels Underpin Hemostasis and Thrombosis

Molecular and Phenotypic Characterization of Human Amniotic Fluid-Derived Cells: A Morphological and Proteomic Approach

Effects of moderate electrical stimulation on reactive species production by primary rat skeletal muscle cells: Cross talk between superoxide and nitric oxide production

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