The polyamines regulate endothelial cell survival during hypoxic stress through PI3K/AKT and MCL-1.
(2009) In Biochemical and Biophysical Research Communications 380(2). p.413-418- 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,... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1368137
- author
- Kucharzewska, Paulina LU ; Welch, Johanna LU ; Svensson, Katrin LU and Belting, Mattias LU
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Biochemical and Biophysical Research Communications
- volume
- 380
- issue
- 2
- pages
- 413 - 418
- publisher
- Elsevier
- external identifiers
-
- wos:000263742200039
- pmid:19250631
- scopus:60349121139
- ISSN
- 1090-2104
- DOI
- 10.1016/j.bbrc.2009.01.097
- language
- English
- LU publication?
- yes
- id
- 11d46aca-5917-4910-8224-854f96329ccb (old id 1368137)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/19250631?dopt=Abstract
- date added to LUP
- 2016-04-04 09:24:42
- date last changed
- 2022-01-29 17:43:56
@article{11d46aca-5917-4910-8224-854f96329ccb, 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.}}, author = {{Kucharzewska, Paulina and Welch, Johanna and Svensson, Katrin and Belting, Mattias}}, issn = {{1090-2104}}, language = {{eng}}, number = {{2}}, pages = {{413--418}}, publisher = {{Elsevier}}, series = {{Biochemical and Biophysical Research Communications}}, title = {{The polyamines regulate endothelial cell survival during hypoxic stress through PI3K/AKT and MCL-1.}}, url = {{http://dx.doi.org/10.1016/j.bbrc.2009.01.097}}, doi = {{10.1016/j.bbrc.2009.01.097}}, volume = {{380}}, year = {{2009}}, }