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Endothelial cells preparing to die by apoptosis initiate a program of transcriptome and glycome regulation
Author(s) -
Johnson Nicola A.,
Sengupta Shiladitya,
Saidi Samir A.,
Lessan Khashayar,
CharnockJones Stephen D.,
Scott Laurie,
Stephens Richard,
Freeman Tom C.,
Tom Brian D. M.,
Harris Michael,
Denyer Gareth,
Sundaram Mallik,
Sasisekharan Ram,
Smith Stephen K.,
Print Cristin G.
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-0097fje
Subject(s) - glycome , transcriptome , microbiology and biotechnology , apoptosis , programmed cell death , biology , cell , signal transduction , extracellular matrix , phagocytosis , gene expression , biochemistry , glycan , gene , glycoprotein
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.