Mechanism of apoptosis in HL-60 cells induced by n-3 and n-6 polyunsaturated fatty acids 1 1Abbreviations: AA, arachidonic acid; CsA, cyclosporin A; Cyt.c, cytochrome c; DCFH-DA, 2′,7′-dichlorofluorescein diacetate; DPA, docosapentaenoic acid; EPA, eicosapentaenoic acid; HE, hydroethidine; JC-1, 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazol carbocyanine iodide; MPT, membrane permeability transition; PUFA, polyunsaturated fatty acid; ROS, reactive oxygen species; and z-VAD-fmk, z-Val-Ala-Asp(OMe)-fluoromethylketone.

2001 â—½  
Vol 62 (7) â—½  
pp. 821-828 â—½  
Author(s):  
Kayo Arita â—½  
Hirotsugu Kobuchi â—½  
Toshihiko Utsumi â—½  
Yoshiki Takehara â—½  
Jitsuo Akiyama â—½  
...  
Keyword(s):  
Reactive Oxygen Species â—½  
Fatty Acids â—½  
Arachidonic Acid â—½  
Fatty Acid â—½  
Docosapentaenoic Acid â—½  
Permeability Transition â—½  
Oxygen Species â—½  
Membrane Permeability Transition â—½  
Dichlorofluorescein Diacetate â—½  
Ros Reactive Oxygen Species

scholarly journals Arachidonic acid stimulates TNFα production in Kupffer cells via a reactive oxygen species-pERK1/2-Egr1-dependent mechanism

2012 â—½  
Vol 303 (2) â—½  
pp. G228-G239 â—½  
Author(s):  
Francisco Javier Cubero â—½  
Natalia Nieto
Keyword(s):  
Reactive Oxygen Species â—½  
Fatty Acids â—½  
Arachidonic Acid â—½  
Liver Disease â—½  
Nadph Oxidase â—½  
Alcoholic Liver Disease â—½  
Kupffer Cells â—½  
Acid Metabolism â—½  
Arachidonic Acid Metabolism â—½  
Oxygen Species

Kupffer cells are a key source of mediators of alcohol-induced liver damage such as reactive oxygen species, chemokines, growth factors, and eicosanoids. Since diets rich in polyunsaturated fatty acids are a requirement for the development of alcoholic liver disease, we hypothesized that polyunsaturated fatty acids could synergize with ethanol to promote Kupffer cell activation and TNFα production, hence, contributing to liver injury. Primary Kupffer cells from control and from ethanol-fed rats incubated with arachidonic acid showed similar proliferation rates than nontreated cells; however, arachidonic acid induced phenotypic changes, lipid peroxidation, hydroperoxides, and superoxide radical generation. Similar effects occurred in human Kupffer cells. These events were greater in Kupffer cells from ethanol-fed rats, and antioxidants and inhibitors of arachidonic acid metabolism prevented them. Arachidonic acid treatment increased NADPH oxidase activity. Inhibitors of NADPH oxidase and of arachidonic acid metabolism partially prevented the increase in oxidant stress. Upon arachidonic acid stimulation, there was a rapid and sustained increase in TNFα, which was greater in Kupffer cells from ethanol-fed rats than in Kupffer cells from control rats. Arachidonic acid induced ERK1/2 phosphorylation and nuclear translocation of early growth response-1 (Egr1), and ethanol synergized with arachidonic acid to promote this effect. PD98059, a mitogen extracellular kinase 1/2 inhibitor, and curcumin, an Egr1 inhibitor, blocked the arachidonic acid-mediated upregulation of TNFα in Kupffer cells. This study unveils the mechanism whereby arachidonic acid and ethanol increase TNFα production in Kupffer cells, thus contributing to alcoholic liver disease.

scholarly journals Conjugated linoleic acid, unlike other unsaturated fatty acids, strongly induces glutathione synthesis without any lipoperoxidation

10.1017/bjn20061910 â—½  
2006 â—½  
Vol 96 (5) â—½  
pp. 811-819 â—½  
Author(s):  
Khelifa Arab â—½  
Adrien Rossary â—½  
Laurent Soulère â—½  
Jean-Paul Steghens
Keyword(s):  
Reactive Oxygen Species â—½  
Fatty Acids â—½  
Arachidonic Acid â—½  
Linoleic Acid â—½  
Conjugated Linoleic Acid â—½  
Reactive Oxygen â—½  
Redox Status â—½  
Cyclooxygenase 2 â—½  
Cytotoxicity Test â—½  
Oxygen Species

Enhancement of the redox status of cells is a cytoprotective strategy against oxidative damage. We recently showed that DHA upregulates glutathione (GSH) content via an induction of its related enzymes γ-glutamylcysteine ligase and glutathione reductase. In the present study, we investigated the effects of eight other fatty acids on the redox status and lipid peroxidation of human fibroblasts. After 48 h, only arachidonic acid and conjugated linoleic acid (CLA) enhanced GSH content through an induction of γ-glutamylcysteine ligase. CLA was more potent than arachidonic acid in inducing GSH synthesis. For all the fatty acids tested, lipoperoxidation, estimated by cell malondialdehyde measurement, did not differ from that of controls at 48 h but dramatically increased at 7 d, except for CLA. Lipoperoxidation is associated at 7 d with a high level of reactive oxygen species and with increased haemoxygenase-1 and cyclooxygenase-2 mRNA expression. As demonstrated by a tert-butylhydroperoxide cytotoxicity test, the GSH synthesis obtained with arachidonic acid is not sufficient to protect the cells, whereas this protective effect was obvious with CLA at 48 h as well as at 7 d. The present results show that CLA is the only PUFA able to induce GSH synthesis without any change in oxidative balance, whereas an upregulation of cyclooxygenase-2 by other PUFA is concomitant with an overproduction of malondialdehyde and reactive oxygen species. The particular hairpin conformation obtained for CLA by molecular modelling could account for this specific biological effect.

scholarly journals Arachidonic acid- and prostaglandin E2-induced cerebral vasodilation is mediated by carbon monoxide, independent of reactive oxygen species in piglets

2011 â—½  
Vol 301 (6) â—½  
pp. H2482-H2487 â—½  
Author(s):  
Alie Kanu â—½  
Charles W. Leffler
Keyword(s):  
Reactive Oxygen Species â—½  
Carbon Monoxide â—½  
Arachidonic Acid â—½  
Reactive Oxygen â—½  
Oxygen Species â—½  
Artificial Cerebrospinal Fluid â—½  
Newborn Pigs â—½  
Cerebral Vasodilation â—½  
Prostacyclin Analog â—½  
Cerebral Vascular

Arachidonic acid (AA) and prostaglandin (PG) E2 stimulate carbon monoxide (CO) production, and AA metabolism is known to be associated with the generation of reactive oxygen species (ROS). This study was conducted to address the hypothesis that CO and/or ROS mediate cerebrovascular dilation in newborn pigs. Experiments were performed on anesthetized newborn pigs with closed cranial windows. Different concentrations of AA (10−8-10−6 M), PGE2 (10−8-10−6 M), iloprost (10−8-10−6 M), and their vehicle (artificial cerebrospinal fluid) were given. Piglets with PGE2 and iloprost received indomethacin (5 mg/kg iv) to inhibit cyclooxygenase. AA, PGE2, and iloprost caused concentration-dependent increases in pial arteriolar diameter. The effects of both AA and PGE2 in producing cerebral vascular dilation and associated CO production were blocked by the heme oxygenase inhibitor chromium mesoporphyrin (2 × 10−5 M), but not by the prostacyclin analog, iloprost. ROS inhibitor tempol (SOD mimetic) (1 × 10−5 M) and the H2O2 scavenger catalase (1,000 U/ml) also do not block these vasodilator effects of AA and PGE2. Heme-l-lysinate-induced cerebrovascular dilation and CO production was blocked by chromium mesoporphyrin. Hypoxanthine plus xanthine oxidase, a combination that is known to generate ROS, caused pial arteriolar dilation and CO production that was inhibited by tempol and catalase. These data suggest that AA- and PGE2-induced cerebral vascular dilation is mediated by CO, independent of ROS.

Fatty acids as modulators of the cellular production of reactive oxygen species

2008 â—½  
Vol 45 (3) â—½  
pp. 231-241 â—½  
Author(s):  
Peter Schönfeld â—½  
Lech Wojtczak
Keyword(s):  
Reactive Oxygen Species â—½  
Fatty Acids â—½  
Reactive Oxygen â—½  
Oxygen Species
Sign in / Sign up

Export Citation Format

Share Document