Endothelial cells preparing to die by apoptosis initiate a program of transcriptome and glycome regulation.
The protein-based changes that underlie the cell biology of apoptosis have been extensively studied. In contrast, mRNA- and polysaccharide-based changes have received relatively little attention. We have combined transcriptome and glycome analyses to show that apoptotic endothelial cell cultures undergo programmed changes to RNA transcript abundance and cell surface polysaccharide profiles. Although a few of the transcriptome changes were protective, most appeared to prepare cells for apoptosis by decreasing the reception and transduction of pro-survival signals, increasing pro-death signals, increasing abundance of apoptotic machinery, inhibiting cellular proliferation, recruiting phagocytes to regions of cell death, and promoting phagocytosis. Additional transcriptomal changes appeared to alter the synthesis and modification of cell surface glycosaminoglycans. The resultant reduced abundance of sulphated cell surface glycosaminoglycans may further promote cell death by inhibiting the presentation of extracellular matrix-tethered survival factors to their receptors on dying cells. We propose that the transcriptome and glycome regulation presented here synergize with previously described protein-based changes to guide the apoptotic program.
Johnson
Nicola A
NA
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Sengupta
Shiladitya
S
Saidi
Samir A
SA
Lessan
Khashayar
K
Charnock-Jones
Stephen D
SD
Scott
Laurie
L
Stephens
Richard
R
Freeman
Tom C
TC
Tom
Brian D M
BD
Harris
Michael
M
Denyer
Gareth
G
Sundaram
Mallik
M
Sasisekharan
Ram
R
Smith
Stephen K
SK
Print
Cristin G
CG
D017209:Apoptosis; D002470:Cell Survival; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020411:Oligonucleotide Array Sequence Analysis; D010587:Phagocytosis; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic
D019812:Heparan Sulfate Proteoglycans; D011506:Proteins; D012333:RNA, Messenger