Fatty acids decrease catalase activity in human leukaemia cell lines

Azevedo-Martins, Anna Karenina; Curi, Rui

doi:10.1002/cbf.1404

Cited by 17 publications

(8 citation statements)

References 48 publications

(36 reference statements)

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“…There are several studies regarding downstream effects of fatty acids. These studies focus mainly on the effects of OA, LA, or PA on resting human T-cells ( 36 ) or Jurkat cells (T-cell leukemia cell line) ( 31 , 34 , 37 , 51 , 52 ). As previously mentioned fatty acids can influence T-cells in a dose-dependent manner, with low doses modulating proliferation and higher doses inducing apoptosis.…”

Section: Downstream Effects Of Fatty Acidsmentioning

confidence: 99%

“…Several apoptotic characteristics are induced by fatty acids in T-cells, such as mitochondrial depolarization ( 31 , 34 ), caspase activation ( 34 , 37 ), DNA fragmentation ( 31 , 34 ), chromatin condensation ( 31 ), cytochrome c ( 34 ), and phosphatidylserine externalization ( 31 ), indicating that T-cells treated with high-concentrations fatty acids die due to apoptosis. In addition, T-cells incubated with fatty acids also induce oxidative and nitrosative stress leading to apoptosis, indicated by higher levels of reactive oxygen species (ROS), reactive nitrogen species, and lower levels of catalase activity ( 34 , 51 , 52 ).…”

Section: Downstream Effects Of Fatty Acidsmentioning

confidence: 99%

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Fatty Acids, Lipid Mediators, and T-Cell Function

et al. 2014

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Research toward the mechanisms underlying obesity-linked complications has intensified during the last years. As a consequence, it has become clear that metabolism and immunity are intimately linked. Free fatty acids and other lipids acquired in excess by current feeding patterns have been proposed to mediate this link due to their immune modulatory capacity. The functional differences between saturated and unsaturated fatty acids, in combination with their dietary intake are believed to modulate the outcome of immune responses. Moreover, unsaturated fatty acids can be oxidized in a tightly regulated and specific manner to generate either potent pro-inflammatory or pro-resolving lipid mediators. These oxidative derivatives of fatty acids have received detailed attention during the last years, as they have proven to have strong immune modulatory capacity, even in pM ranges. Both fatty acids and oxidized fatty acids have been studied especially in relation to macrophage and T-cells functions. In this review, we propose to focus on the effect of fatty acids and their oxidative derivatives on T-cells, as it is an active area of research during the past 5 years. The effect of fatty acids and their derivatives on activation and proliferation of T-cells, as well as the delicate balance between stimulation and lipotoxicity will be discussed. Moreover, the receptors involved in the interaction between free fatty acids and their derivatives with T-cells will be summarized. Finally, the mechanisms involved in modulation of T-cells by fatty acids will be addressed, including cellular signaling and metabolism of T-cells. The in vitro results will be placed in context of in vivo studies both in humans and mice. In this review, we summarize the latest findings on the immune modulatory function of lipids on T-cells and will point out novel directions for future research.

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Section: Downstream Effects Of Fatty Acidsmentioning

confidence: 99%

Section: Downstream Effects Of Fatty Acidsmentioning

confidence: 99%

Fatty Acids, Lipid Mediators, and T-Cell Function

et al. 2014

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“…These observations suggest that PLA 2 enzyme‐induced signalling pathways are cell type specific. Previous studies have reported that U937 and K562 cells have different membrane phospholipid compositions and that fatty acids activate different death pathways in these leukaemia cells 16,26,29–31 . A combination of LPC and stearic acid mimics the effect of CMS‐9 on K562 cells, 12 whereas cotreatment with LPC and palmitic acid acts in a manner similar to CMS‐9 on U937 cells.…”

Section: Discussionmentioning

confidence: 96%

“…The ethanol concentration in the medium was always < 0.5% of the final volume of cell suspension. The viability of cells treated with fatty acid and LPC (both at concentrations of 0–100 μmol/L) was assessed by Trypan blue exclusion assay according to the method of Azevedo‐Martins and Curi 16 …”

Section: Methodsmentioning

confidence: 99%

Naja nigricollis CMS-9 enhances the mitochondria-mediated death pathway in adaphostin-treated human leukaemia U937 cells

Chen

Wang

Chang

2011

Clinical and Experimental Pharmacology and Physiology

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1. The aim of the present study was to explore the effect of the Naja nigricollis phospholipase A(2) CMS-9 on adaphostin-induced death of human leukaemia U937 cells. 2. Leukaemia U937 cells (Bcr/Abl-negative cells) were treated with adaphostin (0-10 μmol/L) and CMS-9 (0-1 μmol/L). The effects of CMS-9, adaphostin and their combination on cell viability, the generation reactive oxygen species (ROS), [Ca(2+) ](i) , p38 mitogen-activated protein kinase (MAPK) activation, Akt and extracellular signal-regulated kinase (ERK) inactivation, mitochondrial membrane potential (ΔΨ(m) ) and Bcl-2 family proteins were analysed. 3. Both adaphostin and CMS-9 induced U937 cell apoptosis, characterized by dissipation of ΔΨ(m) and ROS generation. Combined treatment further increased ΔΨ(m) loss and reduced the viability of adaphostin-treated cells. Unlike in CMS-9-treated cells, in adaphostin-treated cells ROS-induced increases in [Ca(2+) ](i) were observed. CMS-9-induced ROS generation resulted in p38 MAPK activation, whereas adaphostin treatment elicited ROS/Ca(2+) -mediated inactivation of Akt and ERK. Moreover, Akt was found to be involved in ERK phosphorylation. Suppression of p38 MAPK activation blocked CMS-9-induced ΔΨ(m) loss and Bcl-xL downregulation. Overexpression of constitutively active Akt and mitogen-activated protein kinase kinase (MEK) 1 rescued adaphostin-induced ΔΨ(m) loss and Bcl-2 downregulation. Similarly, CMS-9 augmented adaphostin toxicity in human leukaemia K562 cells via increased mitochondrial alterations. 4. The results suggest that two distinct pathways mediate adaphostin- and CMS-9-induced mitochondrial damage (i.e. the ROS-Ca(2+) -Akt-ERK and ROS-p38 MAPK pathways, respectively). These distinct pathway explain the augmentation by CMS-9 of ΔΨ(m) loss and apoptosis in adaphostin-treated U937 cells.

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“…5B). Similarly it was recently reported that fatty acids decrease catalase activities without altering protein or RNA levels [38]. The catalase increased activities are mediated selectively through the B isoform of progesterone receptor and the progestin effect on hydrogen peroxide was restricted to the clones expressing PRB.…”

Section: Discussionmentioning

confidence: 97%