Endothelial cells preparing to die by apoptosis initiate a program of transcriptome and glycome regulation

Nicola A Johnson, Shiladitya Sengupta, Samir A Saidi, Khashayar Lessan, Stephen D Charnock-Jones, Laurie Scott, Richard Stephens, Tom C Freeman, Brian D M Tom, Michael Harris, Gareth Denyer, Mallik Sundaram, Ram Sasisekharan, Stephen K Smith, Cristin G Print

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)188-90
Number of pages3
JournalThe FASEB Journal
Volume18
Issue number1
DOIs
Publication statusPublished - Jan 2004

Keywords

  • Apoptosis
  • Cell Survival
  • Cells, Cultured
  • Endothelium, Vascular
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Heparan Sulfate Proteoglycans
  • Humans
  • Immunohistochemistry
  • Oligonucleotide Array Sequence Analysis
  • Phagocytosis
  • Polymerase Chain Reaction
  • Protein Biosynthesis
  • Proteins
  • RNA, Messenger
  • Transcription, Genetic

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