Phosphoinositide 3-kinase β, phosphoinositide 3-kinase δ, and phosphoinositide 3-kinase γ mediate the anti-inflammatory effects of magnesium sulfate

Lee, Ping Ying; Yang, Chen; Kao, Ming‐Chien; Su, Nuan Yen; Tsai, Pei Shan; Huang, Chun Jen

doi:10.1016/j.jss.2015.04.051

Cited by 14 publications

(5 citation statements)

References 32 publications

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“…This phenomenon might also be one of the mechanisms underlying the inhibitory effect of Mg PIII treatment on M1 macrophage differentiation 23 24 . L-type calcium channels, phosphoinositide 3-kinase/Akt and phosphoinositide 3-kinase β, δ, and γ are involved in the anti-inflammation effects of Mg 25 26 27 . The exact molecular mechanisms whereby Mg affects macrophage polarization and inflammation need to be investigated further.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: In vitro and in vivo responses of macrophages to magnesium-doped titanium

Cao

Zhao

et al. 2017

Sci Rep

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Modulating immune response to biomaterials through changing macrophage polarization has been proven to be a promising strategy to elicit beneficial outcomes in tissue repair. The objective of this study was to evaluate the response of macrophage polarization to titanium doped with magnesium (0.1~0.35%), which was prepared through the magnesium plasma immersion ion implantation (Mg PIII) technique. The M1/M2 polarization profile of macrophages was investigated using a murine cell line RAW 264.7 in vitro and a murine air pouch model in vivo. Our results demonstrated that the Mg PIII-treated titanium induced a higher percentage of M2 macrophages and higher concentrations of the anti-inflammatory cytokines interleukin (IL)-4 and IL-10. Genes encoding two growth factors, bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF) were up-regulated, thus indicating the ability of the M2 phenotype to promote wound healing. The nuclear factor κB (NF-κB) signalling pathway was down-regulated. In vivo the Mg PIII -treated titanium elicited a similar effect on macrophage polarization and induced thinner fibrous capsule formation and a decrease in infiltrated cells. These results indicate that Mg PIII treatment has the immunomodulatory potential to elicit the pro-healing M2-polarized macrophage phenotype, thus providing new insight into the development of immunomodulatory biomaterials.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: In vitro and in vivo responses of macrophages to magnesium-doped titanium

Cao

Zhao

et al. 2017

Sci Rep

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“…Significantly, the phosphorylation of Ser 473 alone has little effect on Akt/PKB activity [ 35 , 36 ]. Several studies have implicated Mg 2+ in the regulation of Akt/PKB activity [ 37 , 38 ]. Krueger et al have demonstrated that elevated [Mg 2+ ] e (3.3 mM) increases cell proliferation in neural cells in culture and have observed that increased Akt/PKB activation, comparable with activation by INS (200 nM), follows Mg 2+ treatment [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Na+/Mg2+ exchanger SLC41A1 attenuates pro-survival signaling

et al. 2017

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The Na+/Mg2+ exchanger SLC41A1 (A1), a key component of intracellular Mg homeostasis (IMH), is the major cellular Mg2+ efflux system, and its overexpression decreases [Mg2+]intracellular. IMH plays an important role in the regulation of many cellular processes, including cellular signaling. However, whether the overexpression of A1 and the consequent drop of [Mg2+]i impact on intracellular signaling is unknown.To examine the latter, we utilized dynamic mass redistribution (DMR) assay, PathScan® RTK signaling antibody (PRSA) array, confirmatory Western blot (WB) analyses of phosphorylation of kinases selected by PRSA, and mag-fura 2-assisted fast filter spectrometry (FFS).We demonstrate here that the overexpression of A1 quantitatively and qualitatively changes the DMR signal evoked by the application of PAR-1-selective activating peptide and/or by changing [Mg2+]extracellular in HEK293 cells. PRSA profiling of the phosphorylation of important signaling nodes followed by confirmatory WB has revealed that, in HEK293 cells, A1 overexpression significantly attenuates the phosphorylation of Akt/PKB on Thr308 and/or Ser473 and of Erk1/2 on Thr202/Tyr204 in the presence of 0 or 1 mM (physiological) Mg2+ in the bath solution. The latter is also true for SH-SY5Y and HeLa cells. Overexpression of A1 in HEK293 cells significantly lowers [Mg2+]i in the presence of [Mg2+]e = 0 or 1 mM. This correlates with the observed attenuation of prosurvival Akt/PKB – Erk1/2 signaling in these cells.Thus, A1 expression status and [Mg2+]e (and consequently also [Mg2+]i) modulate the complex physiological fingerprint of the cell and influence the activity of kinases involved in anti-apoptotic and, hence, pro-survival events in cells.

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“…When the insulin concentration is low in cells, due to insulin resistance, phosphatidylinositol phosphates are formed by phosphatidylinositol-3-kinase (PI3K), that are activated by tyrosine kinase to elevate glucose uptake (Smith and Morton 2010). Previous literatures revealed that the magnesium ions have the ability to activate both these enzymes in preadipocytes (Ha et al 2016;Lee et al 2015;Yang et al 2000). Hence, it has been proposed in the current study that the magnesium ions from the nanoparticles may activate these enzymes, which may have subsequently activated GLUT-4 to increase glucose uptake.…”

Section: Insulin Resistance Reversal Analysis Via Colorimetric Glucose Assaymentioning

confidence: 99%

Cytotoxicity and insulin resistance reversal ability of biofunctional phytosynthesized MgO nanoparticles

2020

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The present study investigates the cytotoxicity of hexagonal MgO nanoparticles synthesized via Amaranthus tricolor leaf extract and spherical MgO nanoparticles synthesized via Amaranthus blitum and Andrographis paniculata leaf extracts. In vitro cytotoxicity analysis showed that the hexagonal MgO nanoparticles synthesized from A. tricolor extract demonstrated the least toxicity to both diabetic and non-diabetic cells at 600 μl/ml dosage. The viability of the diabetic cells (3T3-L1) after incubation with varying dosages of MgO nanoparticles was observed to be 55.3%. The viability of normal VERO cells was 86.6% and this stabilized to about 75% even after exposure to MgO nanoparticles dosage of up to 1000 μl/ml. Colorimetric glucose assay revealed that the A. tricolor extract synthesized MgO nanoparticles resulted in ~ 28% insulin resistance reversal. A reduction in the expression of GLUT4 protein at 54 KDa after MgO nanopaSrticles incubation with diabetic cells was observed via western blot analysis to confirm insulin reversal ability. Fluorescence microscopic analysis with propidium iodide and acridine orange dyes showed the release of reactive oxygen species as a possible mechanism of the cytotoxic effect of MgO nanoparticles. It was inferred that the synergistic effect of the phytochemicals and MgO nanoparticles played a significant role in delivering enhanced insulin resistance reversal capability in adipose cells.

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Phosphoinositide 3-kinase β, phosphoinositide 3-kinase δ, and phosphoinositide 3-kinase γ mediate the anti-inflammatory effects of magnesium sulfate

Cited by 14 publications

References 32 publications

RETRACTED ARTICLE: In vitro and in vivo responses of macrophages to magnesium-doped titanium

RETRACTED ARTICLE: In vitro and in vivo responses of macrophages to magnesium-doped titanium

Overexpression of Na+/Mg2+ exchanger SLC41A1 attenuates pro-survival signaling

Cytotoxicity and insulin resistance reversal ability of biofunctional phytosynthesized MgO nanoparticles

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