Journal ArticleDOI
Fatty acid oxidation and signaling in apoptosis.
TLDR
The effects of fatty acids and fatty acid oxidation products on signal transduction pathways, particularly those involved in apoptosis, can be considered in terms of their overall importance relative to the much better studied protein or peptide signaling factors.Abstract:
It is well established that fatty acid metabolites of cyclooxygenase, lipoxygenase (LOX), and cytochrome P450 are implicated in essential aspects of cellular signaling including the induction of programmed cell death Here we review the roles of enzymatic and non-enzymatic products of polyunsaturated fatty acids in controlling cell growth and apoptosis Also, the spontaneous oxidation of polyunsaturated fatty acids yields reactive aldehydes and other products of lipid peroxidation that are potentially toxic to cells and may also signal apoptosis Significant conflicting data in terms of the role of LOX enzymes are highlighted, prompting a re-evaluation of the relationship between LOX and prostate cancer cell survival We include new data showing that LNCaP, PC3, and Du145 cells express much lower levels of 5-LOX mRNA and protein compared with normal prostate epithelial cells (NHP2) and primary prostate carcinoma cells (TP1) Although the 5-LOX activating protein inhibitor MK886 killed these cells, another 5-LOX inhibitor AA861 hardly showed any effect These observations suggest that 5-LOX is unlikely to be a prostate cancer cell survival factor, implying that the mechanisms by which LOX inhibitors induce apoptosis are more complex than expected This review also suggests several mechanisms involving peroxisome proliferator activated receptor activation, BCL proteins, thiol regulation, and mitochondrial and kinase signaling by which cell death may be produced in response to changes in non-esterified and non-protein bound fatty acid levels Overall, this review provides a context within which the effects of fatty acids and fatty acid oxidation products on signal transduction pathways, particularly those involved in apoptosis, can be considered in terms of their overall importance relative to the much better studied protein or peptide signaling factorsread more
Citations
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Journal ArticleDOI
Role of oxygen radicals in DNA damage and cancer incidence
TL;DR: The epidemiological trials together with in vitro experiments suggest that the optimal approach is to reduce endogenous and exogenous sources of oxidative stress, rather than increase intake of anti-oxidants.
Journal ArticleDOI
Rapid Induction of Distinct Stress Responses after the Release of Singlet Oxygen in Arabidopsis
Roel op den Camp,Dominika Przybyla,Christian Ochsenbein,Christophe Laloi,Chanhong Kim,Antoine Danon,Daniela Wagner,Éva Hideg,Cornelia Göbel,Ivo Feussner,Mena Nater,Klaus Apel +11 more
TL;DR: Results demonstrate that singlet oxygen does not act primarily as a toxin but rather as a signal that activates several stress-response pathways and its biological activity in Arabidopsis exhibits a high degree of specificity that seems to be derived from the chemical identity of this reactive oxygen species and/or the intracellular location at which it is generated.
Journal ArticleDOI
Biological significance of phospholipid hydroperoxide glutathione peroxidase (PHGPx, GPx4) in mammalian cells.
Hirotaka Imai,Yasuhito Nakagawa +1 more
TL;DR: This review focuses on the structure and biological functions of PHGPx in mammalian cells, which has become clear that lipid hydroperoxides also have an important function as activators of lipoxygenase and cyclooxygenases, participate in inflammation, and act as signal molecules for apoptotic cell death and receptor-mediated signal transduction at the cellular level.
Journal ArticleDOI
De novo Lipogenesis Protects Cancer Cells from Free Radicals and Chemotherapeutics by Promoting Membrane Lipid Saturation
Evelien Rysman,Koen Brusselmans,Katryn Scheys,Leen Timmermans,Rita Derua,Sebastian Munck,Paul P. Van Veldhoven,David Waltregny,Veerle W. Daniels,Jelle Machiels,Frank Vanderhoydonc,Karine Smans,Etienne Waelkens,Guido Verhoeven,Johannes V. Swinnen +14 more
TL;DR: Evidence is provided that shifting lipid acquisition from lipid uptake toward de novo lipogenesis dramatically changes membrane properties and protects cells from both endogenous and exogenous insults, and provides a rationale for the use of lipogenesis inhibitors as antineoplastic agents and as chemotherapeutic sensitizers.
Journal ArticleDOI
Fatty acid oxidation is a dominant bioenergetic pathway in prostate cancer.
TL;DR: Dominant fatty acid metabolism rather than glycolysis has the potential to be the basis for imaging diagnosis and targeted treatment of prostate cancer.
References
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Journal ArticleDOI
Mitochondria and apoptosis
Douglas R. Green,John C. Reed +1 more
TL;DR: A variety of key events in apoptosis focus on mitochondria, including the release of caspase activators (such as cytochrome c), changes in electron transport, loss of mitochondrial transmembrane potential, altered cellular oxidation-reduction, and participation of pro- and antiapoptotic Bcl-2 family proteins.
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TL;DR: This work has shown that understanding caspase regulation is intimately linked to the ability to rationally manipulate apoptosis for therapeutic gain.
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TL;DR: This review provides a comprehensive summary on the chemical properties of 4-hydroxyalkenals and malonaldehyde, the mechanisms of their formation and their occurrence in biological systems and methods for their determination, as well as the many types of biological activities described so far.
Journal ArticleDOI
The Bcl-2 Protein Family: Arbiters of Cell Survival
Jerry M. Adams,Suzanne Cory +1 more
TL;DR: Bcl-2 and related cytoplasmic proteins are key regulators of apoptosis, the cell suicide program critical for development, tissue homeostasis, and protection against pathogens.
Journal ArticleDOI
Apoptosis by death factor.
TL;DR: This work was supported in part by Grants-in-Aid from the Ministry of Education, Science, and Culture of Japan and by a Research Grant from the Princess Takamatsu Cancer Research Fund, and performed in part through Special Coordination Funds of the Science and Technology Agency of the Japanese Government.