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

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.

Caspases shutdown nonsense-mediated mRNA decay during apoptosis

“…However, this contribution to apoptosis appears to be modest and is likely due to the wide spectrum of caspase targets that influence apoptosis. [3][4][5] Further investigations will be necessary to elucidate the mechanism underlying the induction of apoptosis by these UPF cleavage fragments, to identify the proteins that bind these fragments and in particular the highly conserved N-terminal UPF1 fragment for which there is, as yet, no clear function. With respect to UPF2, specific functions have not been correlated with the different regions of UPF2 other than the interaction domain in the C-terminal region with UPF1 and SMG1.…”

“…1 Cell death can occur via programed processes such as apoptosis, autophagy, necrosis (a more passive process) or necroptosis (a type of programed necrosis). 2 During apoptosis, specific gene networks and proteincleavage programs are activated sending the cells on a death spiral [3][4][5] through a family of cysteine-aspartate proteases (caspases). 6 Caspases are classified by their role in the apoptotic pathway, into (i) initiator caspases (such as caspases2, 8, 9 and 10) or (ii) effector caspases (such as caspases3, 6 or 7).…”

Bioinformatic analysis of primary endothelial cell gene array data illustrated by the analysis of transcriptome changes in endothelial cells exposed to VEGF-A and PlGF

“…While the incidence of apoptosis in HUVEC cultured in rich medium is low (1 to 2%), it is significantly elevated when these cells are cultured in low serum medium for 24 h (9 to 15%; [25]). Neither this serum deprivation-induced apoptosis nor total cell number was significantly altered by the addition to low serum media of 10 ng/ml VEGF-A 165 for 4 h (ANOVA P > 0.05; data not shown).…”

Morphological and molecular changes of the myocardium after left ventricular mechanical support

“…They are expressed on numerous cell types in the cardiovascular system and are involved in gene expression, cell migration, cell proliferation, differentiation and cell death. Moreover, they have been shown to have function in mechanotransduction (cellular mechanism by which a mechanical stimulus is converted in a chemical signal) in response to physiological and pathophysiological signals [125][126][127]. Integrins bind directly to components of the cytoskeleton through their cytoplasmic tails and can orchestrate changes in cellular architecture.…”