@article {Abboud66, author = {Elizabeth R. Abboud and Bryan D. Shelby and Magdalena Angelova and Anne B. Nelson and MaryBeth Ferris and Harris E. McFerrin and Cindy A. Morris and Deborah E. Sullivan}, title = {Kaposi Sarcoma{\textendash}Associated Herpesvirus G Protein{\textendash}Coupled Receptor Enhances Endothelial Cell Survival in Part by Upregulation of Bcl-2}, volume = {13}, number = {1}, pages = {66--75}, year = {2013}, publisher = {Ochsner Journal}, abstract = {Background Kaposi sarcoma{\textendash}associated herpesvirus (KSHV) encoded G protein{\textendash}coupled receptor (vGPCR) is a constitutively active lytic phase protein with significant homology to the human interleukin-8 receptor. vGPCR is necessary and sufficient to induce angiogenesis as well as the spindle cell proliferation characteristic of Kaposi sarcoma (KS) lesions. We previously demonstrated that Bcl-2, an antiapoptotic protein, is upregulated in KS lesions. The aim of this study was to determine if vGPCR enhances endothelial cell survival through upregulation of Bcl-2 expression and to elucidate the signaling pathways involved.Methods Primary human umbilical vein endothelial cells were transduced with a recombinant retrovirus expressing vGPCR and then subjected to serum starvation. Cell viability and apoptosis were analyzed by fluorescence-activated cell sorting. Bcl-2 expression was determined by real-time quantitative reverse transcription polymerase chain reaction and immunoblotting. Specific pharmacological inhibitors of phosphatidylinositol 3-kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) were employed to elucidate the signaling pathways involved. Bcl-2 expression was knocked down using small interfering RNA (siRNA).Results Endothelial cells expressing vGPCR showed increased survival after serum starvation and upregulation of Bcl-2 messenger RNA (mRNA) and protein. The vGPCR-induced increases in both Bcl-2 mRNA and protein levels were dependent on PI3K signaling but not on mTOR. Moreover, siRNA inhibition of Bcl-2 resulted in significant abrogation of the observed vGPCR-mediated cell survival advantage.Conclusions Taken together, the results demonstrate that Bcl-2 is a mediator of vGPCR-induced endothelial cell survival and is a downstream effector of Akt in this process.}, issn = {1524-5012}, URL = {https://www.ochsnerjournal.org/content/13/1/66}, eprint = {https://www.ochsnerjournal.org/content/13/1/66.full.pdf}, journal = {Ochsner Journal} }