The polyamines regulate endothelial cell survival during hypoxic stress through PI3K/AKT and MCL-1.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Hypoxia-dependent angiogenesis is an inherent feature of solid tumors, and a better understanding of the molecular mechanisms of hypoxic cell-death should provide additional targets for cancer therapy. Here, we show a novel role of the polyamines in endothelial cell (EC) survival during hypoxia. Polyamine depletion by specific inhibition of ornithine decarboxylase was shown to protect ECs from hypoxia-induced apoptosis. Inhibition of the polyamines resulted in a significant induction of PI3K/AKT and its down-stream target MCL-1, i.e. an anti-apoptotic member of the BCL-2 family. Specific inhibitors of PI3K reversed the decrease of hypoxia-induced apoptosis as well as the induction of MCL-1 in polyamine-deprived cells. Moreover, siRNA-mediated down-regulation of MCL-1 was found to counter-act the protective effect of polyamine inhibition. We conclude that the polyamines regulate hypoxia-induced apoptosis in ECs through PI3K/AKT and MCL-1 dependent pathways. Our results may have important implications for the modulation of hypoxia-driven neovascularization.

Detaljer

Författare
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Biologiska vetenskaper
Originalspråkengelska
Sidor (från-till)413-418
TidskriftBiochemical and Biophysical Research Communications
Volym380
Utgivningsnummer2
StatusPublished - 2009
PublikationskategoriForskning
Peer review utfördJa

Relaterad forskningsoutput

Kucharzewska, P., 2011, Division of Oncology, Department of Clinical Sciences. 162 s.

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

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