Crucial role of HSP90 in the Akt-dependent promotion of angiogenic-like effect of glucose-regulated protein94 (Grp94)-IgG complexes.
Bottom Line: CCT failed to inhibit any morphological alteration induced by Grp94-IgG on HUVECs, on its own displaying a paradoxical angiogenic-like activity.CTT appeared to enhance the angiogenic-like effect of Grp94-IgG by increasing the rate of secretion of both HSP90 and MMP-9.Results reveal a fundamental role of HSP90 in the PI3K/Akt pathway-mediated angiogenic-like effect of Grp94-IgG, also questioning the capacity of CTT to serve as an effective inhibitor of the angiogenic effect.
Affiliation: Department of Pharmacology and Anesthesiology, University of Padova, Largo E. Meneghetti, Padova, Italy.Show MeSH
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Mentions: The effective inhibition by PU-H71 of the HSP90 expression and secretion stimulated by Grp94-IgG would predict antagonism on the angiogenic-like promoting activity of Grp94-IgG. In addition, because MMP-9 is actively involved in the angiogenic process, and its stimulation by Grp94-IgG is mediated by HSP90-dependent Akt activation, it would be expected that the expression of MMP-9 were similarly inhibited by PU-H71. Experiments of zymography showed that PU-H71 at the highest concentration caused a significant reduction in the secretion of MMP-9 pro-form stimulated by Grp94-IgG (Fig. 8). This result indirectly proved that the Akt pathway was involved in the process of MMP-9 transport to the membrane and secretion from the cell that is functional to the diffusion of angiogenesis.
Affiliation: Department of Pharmacology and Anesthesiology, University of Padova, Largo E. Meneghetti, Padova, Italy.