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10.1016/j.jss.2015.04.051 http://scihub22266oqcxt.onion/10.1016/j.jss.2015.04.051 25972311!ä!25972311 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 280.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Surg+Res 2015 ; 197 (2): 390-7 Nephropedia Template TP {{tp|p=25972311|t=2015. Phosphoinositide 3-kinase beta, phosphoinositide 3-kinase delta, and phosphoinositide 3-kinase gamma mediate the anti-inflammatory effects of magnesium sulfate |pdf=|usr=}}{{25972311}} gab.com Text Phosphoinositide 3-kinase beta, phosphoinositide 3-kinase delta, and phosphoinositide 3-kinase gamma mediate the anti-inflammatory effects of magnesium sulfate JO: J Surg Res http://www.kidney.de/pget.php?&tw=1&pmid=25972311 #FOAvip BACKGROUND: We previously demonstrated that inhibiting phosphoinositide 3-kinase (PI3K) or activating L-type calcium channels blocked the anti-inflammatory effects of magnesium sulfate (MgSO(4)). However, the question as which class I PI3K isoform (PI3Kalpha, PI3Kbeta, PI3Kdelta, or PI3Kgamma) is involved in this regard remains unstudied. The question as whether MgSO(4) and L-type calcium channels interact to influence PI3K activation also remains unstudied. We therefore designed this study to test two hypotheses: (1) inhibiting PI3Kalpha, PI3Kbeta, PI3Kdelta, or PI3Kgamma would block the anti-inflammatory effects of MgSO(4) and (2) activating L-type calcium channels would block the effects of MgSO(4) on activating PI3K. MATERIALS AND METHODS: PI3K isoform investigation: macrophages (RAW264.7 cells) were treated with endotoxin, endotoxin plus MgSO(4), or endotoxin plus MgSO(4) plus the selective inhibitor of PI3Kalpha (PIK-75), PI3Kbeta (TGX-221), PI3Kdelta (IC-87114), or PI3Kgamma (AS-252424). Calcium channel investigation: macrophages were treated with endotoxin, endotoxin plus MgSO(4), or endotoxin plus MgSO(4) plus the L-type calcium channel activator BAY-K8644. RESULTS: The endotoxin plus MgSO(4) group presented lower concentrations of inflammatory mediators (macrophage inflammatory protein 2, tumor necrosis factor alpha, and interleukin 6, lower nuclear concentration of phosphorylated nuclear factor kappaB, lower cytosolic concentration of phosphorylated inhibitor kappaBalpha, and higher concentration of phosphorylated Akt (PI3K activation marker) than the endotoxin group (all P < 0.05). These effects of MgSO(4) were significantly reduced by TGX-221, IC-87114, or AS-252424, but not PIK-75. Additionally, BAY-K8644 blocked the effect of MgSO(4) on activating PI3K. CONCLUSIONS: MgSO(4) exerts its anti-inflammatory effects through activating PI3Kbeta, PI3Kdelta, and PI3Kgamma. The underlying mechanism appears to involve inhibition of L-type calcium channels. Twit Text FOAVip Phosphoinositide 3-kinase beta, phosphoinositide 3-kinase delta, and phosphoinositide 3-kinase gamma mediate the anti-inflammatory effects of magnesium sulfate ????J Surg Res http://www.kidney.de/pget.php?&tw=1&pmid=25972311 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25972311 #FOAvip English Wikipedia <ref>{{Cite pmid|25972311}}</ref> Phosphoinositide 3-kinase beta, phosphoinositide 3-kinase delta, and phosphoinositide 3-kinase gamma mediate the anti-inflammatory effects of magnesium sulfate #MMPMID25972311 Lee PY; Yang CH; Kao MC; Su NY; Tsai PS; Huang CJ J Surg Res 2015[Aug]; 197 (2): 390-7 PMID25972311show ga BACKGROUND: We previously demonstrated that inhibiting phosphoinositide 3-kinase (PI3K) or activating L-type calcium channels blocked the anti-inflammatory effects of magnesium sulfate (MgSO(4)). However, the question as which class I PI3K isoform (PI3Kalpha, PI3Kbeta, PI3Kdelta, or PI3Kgamma) is involved in this regard remains unstudied. The question as whether MgSO(4) and L-type calcium channels interact to influence PI3K activation also remains unstudied. We therefore designed this study to test two hypotheses: (1) inhibiting PI3Kalpha, PI3Kbeta, PI3Kdelta, or PI3Kgamma would block the anti-inflammatory effects of MgSO(4) and (2) activating L-type calcium channels would block the effects of MgSO(4) on activating PI3K. MATERIALS AND METHODS: PI3K isoform investigation: macrophages (RAW264.7 cells) were treated with endotoxin, endotoxin plus MgSO(4), or endotoxin plus MgSO(4) plus the selective inhibitor of PI3Kalpha (PIK-75), PI3Kbeta (TGX-221), PI3Kdelta (IC-87114), or PI3Kgamma (AS-252424). Calcium channel investigation: macrophages were treated with endotoxin, endotoxin plus MgSO(4), or endotoxin plus MgSO(4) plus the L-type calcium channel activator BAY-K8644. RESULTS: The endotoxin plus MgSO(4) group presented lower concentrations of inflammatory mediators (macrophage inflammatory protein 2, tumor necrosis factor alpha, and interleukin 6, lower nuclear concentration of phosphorylated nuclear factor kappaB, lower cytosolic concentration of phosphorylated inhibitor kappaBalpha, and higher concentration of phosphorylated Akt (PI3K activation marker) than the endotoxin group (all P < 0.05). These effects of MgSO(4) were significantly reduced by TGX-221, IC-87114, or AS-252424, but not PIK-75. Additionally, BAY-K8644 blocked the effect of MgSO(4) on activating PI3K. CONCLUSIONS: MgSO(4) exerts its anti-inflammatory effects through activating PI3Kbeta, PI3Kdelta, and PI3Kgamma. The underlying mechanism appears to involve inhibition of L-type calcium channels. |Animals[MESH] |Anti-Inflammatory Agents/*pharmacology[MESH] |Calcium Channels, L-Type/*metabolism[MESH] |Cells, Cultured[MESH] |Chemokines/metabolism[MESH] |Class I Phosphatidylinositol 3-Kinases/antagonists & inhibitors/*metabolism[MESH] |Cytokines/metabolism[MESH] |Endotoxins[MESH] |Macrophage Activation[MESH] |Macrophages/*drug effects/metabolism[MESH] |Magnesium Sulfate/*pharmacology[MESH]Phosphoinositide 3-kinase beta, phosphoinositide 3-kinase delta, and p(epmc).pdf DeepDyve Pubget Overpricing