Inhibition of capacitative Ca2+ entry by monosaccharides in J774 macrophages

Academic Article

Abstract

  • We have previously noted that Ca2+ signaling events in J774 macrophages are severely inhibited upon pretreatment of the cells with 2-deoxy-D-glucose (2dGlc) or under Glc-free conditions. Both the ability to generate Ca2+ signals via the IP3 mediated pathway as well as the "capacitative" influx of extracellular Ca2+ were compromised. We have investigated the effects of several other monosaccharides on these cells Glucosamine, mannosamine, and amiprilose were able to mimic the effects of 2dGlc on capacitative Ca2+ entry whereas mannose, GlcNAc, galactose and 3-0-methylglucose were without effect. Glucosamine and mannosamine caused an 8-9% drop in ATP levels while amiprilose and 2dGlc caused the ATP levels to decrease by 20% and 40% respectively We addressed the possibility that these sugars may be altering the activation state of a protein kinase mediated pathway either via a direct inhibition or through reduction in cellular ATP levels. We found that the broad range sereine-threonine protein kinase inhibitor, staurosporine, was able to reverse the inhibition of capacitative Ca2+ influx seen in the presence of 2dGlc. However, inhibition in the presence of mannosamine or glucosamine could not be reversed by staurosporine. Staurosporine itself did not modulate the capacitative entry pathway or the levels of ATP in these cells. K252a, bisindolylmaleimide and H-7 were not able to mimic the effect of staurosporine.
  • Published In

  • The FASEB Journal  Journal
  • Author List

  • Darbha S; Marchase RB
  • Volume

  • 11
  • Issue

  • 3