PMID- 23532945
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20130328
LR  - 20211021
IS  - 1524-5012 (Print)
IS  - 1524-5012 (Linking)
VI  - 13
IP  - 1
DP  - 2013 Spring
TI  - Kaposi sarcoma-associated herpesvirus g protein-coupled receptor enhances 
      endothelial cell survival in part by upregulation of bcl-2.
PG  - 66-75
AB  - BACKGROUND: Kaposi sarcoma-associated herpesvirus (KSHV) encoded G 
      protein-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.
FAU - Abboud, Elizabeth R
AU  - Abboud ER
AD  - Department of Microbiology and Immunology, Tulane University School of Medicine, 
      New Orleans, LA.
FAU - Shelby, Bryan D
AU  - Shelby BD
FAU - Angelova, Magdalena
AU  - Angelova M
FAU - Nelson, Anne B
AU  - Nelson AB
FAU - Ferris, Marybeth
AU  - Ferris M
FAU - McFerrin, Harris E
AU  - McFerrin HE
FAU - Morris, Cindy A
AU  - Morris CA
FAU - Sullivan, Deborah E
AU  - Sullivan DE
LA  - eng
GR  - G12 RR026260/RR/NCRR NIH HHS/United States
GR  - P20 GM103424/GM/NIGMS NIH HHS/United States
GR  - P20 RR016456/RR/NCRR NIH HHS/United States
GR  - R03 HD045768/HD/NICHD NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Ochsner J
JT  - Ochsner journal
JID - 101125795
PMC - PMC3603191
OTO - NOTNLM
OT  - Bcl-2 protein
OT  - G protein-coupled receptor
OT  - Kaposi sarcoma
OT  - human herpesvirus 8
OT  - phosphatidylinositol 3-kinase
COIS- Funding: This study was supported in part by grants from the Louisiana Cancer 
      Research Consortium (DES and HEM), HD045768/HD/NICHD NIH (CAM), 
      P20RR016456/RR/NCRR NIH (HEM), P20GM103424/GM/NIGMS NIH (HEM), and 
      5G12RR026260-03/RR/NCRR NIH (HEM). ERA received support from 
      T32-HL-O7973/HL/NHLBI NIH; ERA and BDS received matching funds from the Tulane 
      Cancer Center.
EDAT- 2013/03/28 06:00
MHDA- 2013/03/28 06:01
PMCR- 2013/03/01
CRDT- 2013/03/28 06:00
PHST- 2013/03/28 06:00 [entrez]
PHST- 2013/03/28 06:00 [pubmed]
PHST- 2013/03/28 06:01 [medline]
PHST- 2013/03/01 00:00 [pmc-release]
AID - TOJ-12-0071 [pii]
PST - ppublish
SO  - Ochsner J. 2013 Spring;13(1):66-75.