scholarly journals Intermembrane Translocation of Photodynamically‐generated Lipid Hydroperoxides: Broadcasting of Redox Damage

Author(s):  
Albert W. Girotti ◽  
Witold Korytowski
Keyword(s):  
Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 45
Author(s):  
Helena Beatriz Ferreira ◽  
Tânia Melo ◽  
Artur Paiva ◽  
Maria do Rosário Domingues

Rheumatoid arthritis (RA) is a highly debilitating chronic inflammatory autoimmune disease most prevalent in women. The true etiology of this disease is complex, multifactorial, and is yet to be completely elucidated. However, oxidative stress and lipid peroxidation are associated with the development and pathogenesis of RA. In this case, oxidative damage biomarkers have been found to be significantly higher in RA patients, associated with the oxidation of biomolecules and the stimulation of inflammatory responses. Lipid peroxidation is one of the major consequences of oxidative stress, with the formation of deleterious lipid hydroperoxides and electrophilic reactive lipid species. Additionally, changes in the lipoprotein profile seem to be common in RA, contributing to cardiovascular diseases and a chronic inflammatory environment. Nevertheless, changes in the lipid profile at a molecular level in RA are still poorly understood. Therefore, the goal of this review was to gather all the information regarding lipid alterations in RA analyzed by mass spectrometry. Studies on the variation of lipid profile in RA using lipidomics showed that fatty acid and phospholipid metabolisms, especially in phosphatidylcholine and phosphatidylethanolamine, are affected in this disease. These promising results could lead to the discovery of new diagnostic lipid biomarkers for early diagnosis of RA and targets for personalized medicine.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii218-ii218
Author(s):  
Patricia Yee ◽  
Yiju Wei ◽  
Soo Yeon Kim ◽  
Tong Lu ◽  
Cynthia Lawson ◽  
...  

Abstract Tumor necrosis indicates poor prognoses in many cancers, including glioblastomas (GBMs). Although thought to result from chronic ischemia, the underlying nature and mechanisms driving the involved cell death remain obscured by lack of animal models recapitulating the extent of necrosis in human GBMs. The molecular and clinical heterogeneity of GBMs adds further complexity. Not all GBMs contain necrosis. Mesenchymal (MES)-GBM, the subtype correlated with worst prognosis and highest treatment resistance, is most closely associated with necrosis. MES-GBM exhibits hyperactivity of transcriptional coactivator with PDZ-binding motif (TAZ), a Hippo tumor suppressive pathway effector whose expression in human GBMs predicts short survival. To elucidate mechanisms driving GBM necrosis, we devised a novel orthotopic mouse model recapitulating human MES-GBM phenotypically and histopathologically by expressing a constitutively-active TAZ mutant (TAZ4SA) in three human GBM cell lines (LN229, U87, and LN18) lacking MES signatures (GBM4SA). GBM4SA mice lived significantly shorter than mice implanted with GBMvector or mutant TAZ unable to bind its downstream effector, TEAD (GBM4SA-S51A). Extensive (≥30% of tumor volume) necrosis was present in GBM4SA mice but not GBMvector or GBM4SA-S51A. In GBM4SA tumors, neutrophils coincide with necrosis temporally and spatially. Neutrophil depletion dampens necrosis. Neutrophils isolated from mouse tumors killed co-cultured tumor cells. Neutrophils induce iron-dependent accumulation of lipid hydroperoxides within tumor cells by transferring myeloperoxidase-containing granules into tumor cells. Inhibiting myeloperoxidase suppresses neutrophil-induced tumor cytotoxicity. Intratumoral glutathione peroxidase 4 (GPX4) overexpression or acyl-CoA synthetase 4 (ACSL4) depletion diminishes necrosis and aggressiveness of tumors. Human GBM analysis indicates neutrophils and ferroptosis are associated with necrosis and predict poor survival. Together, we propose that certain tumor damage(s) during early tumor progression (i.e. ischemia) recruits neutrophils to damaged tissue and results in a positive feedback loop, amplifying GBM necrosis development. We show GBM necrosis involves neutrophil-triggered ferroptosis and reveal an unprecedented pro-tumorigenic role of ferroptosis.


2021 ◽  
Vol 22 (8) ◽  
pp. 4277
Author(s):  
Marija Pinterić ◽  
Iva I. Podgorski ◽  
Marijana Popović Hadžija ◽  
Ivana Tartaro Bujak ◽  
Ana Tadijan ◽  
...  

High fat diet (HFD) is an important factor in the development of metabolic diseases, with liver as metabolic center being highly exposed to its influence. However, the effect of HFD-induced metabolic stress with respect to ovary hormone depletion and sirtuin 3 (Sirt3) is not clear. Here we investigated the effect of Sirt3 in liver of ovariectomized and sham female mice upon 10 weeks of feeding with standard-fat diet (SFD) or HFD. Liver was examined by Folch, gas chromatography and lipid hydroperoxide analysis, histology and oil red staining, RT-PCR, Western blot, antioxidative enzyme and oxygen consumption analyses. In SFD-fed WT mice, ovariectomy increased Sirt3 and fatty acids synthesis, maintained mitochondrial function, and decreased levels of lipid hydroperoxides. Combination of ovariectomy and Sirt3 depletion reduced pparα, Scd-1 ratio, MUFA proportions, CII-driven respiration, and increased lipid damage. HFD compromised CII-driven respiration and activated peroxisomal ROS scavenging enzyme catalase in sham mice, whereas in combination with ovariectomy and Sirt3 depletion, increased body weight gain, expression of NAFLD- and oxidative stress-inducing genes, and impaired response of antioxidative system. Overall, this study provides evidence that protection against harmful effects of HFD in female mice is attributed to the combined effect of female sex hormones and Sirt3, thus contributing to preclinical research on possible sex-related therapeutic agents for metabolic syndrome and associated diseases.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Alexander Beatty ◽  
Tanu Singh ◽  
Yulia Y. Tyurina ◽  
Vladimir A. Tyurin ◽  
Svetlana Samovich ◽  
...  

AbstractFerroptosis is associated with lipid hydroperoxides generated by the oxidation of polyunsaturated acyl chains. Lipid hydroperoxides are reduced by glutathione peroxidase 4 (GPX4) and GPX4 inhibitors induce ferroptosis. However, the therapeutic potential of triggering ferroptosis in cancer cells with polyunsaturated fatty acids is unknown. Here, we identify conjugated linoleates including α-eleostearic acid (αESA) as ferroptosis inducers. αESA does not alter GPX4 activity but is incorporated into cellular lipids and promotes lipid peroxidation and cell death in diverse cancer cell types. αESA-triggered death is mediated by acyl-CoA synthetase long-chain isoform 1, which promotes αESA incorporation into neutral lipids including triacylglycerols. Interfering with triacylglycerol biosynthesis suppresses ferroptosis triggered by αESA but not by GPX4 inhibition. Oral administration of tung oil, naturally rich in αESA, to mice limits tumor growth and metastasis with transcriptional changes consistent with ferroptosis. Overall, these findings illuminate a potential approach to ferroptosis, complementary to GPX4 inhibition.


2015 ◽  
Vol 40 (4) ◽  
pp. 414-423 ◽  
Author(s):  
Phillip G. Bell ◽  
Ian H. Walshe ◽  
Gareth W. Davison ◽  
Emma J. Stevenson ◽  
Glyn Howatson

The impact of Montmorency tart cherry (Prunus cerasus L.) concentrate (MC) on physiological indices and functional performance was examined following a bout of high-intensity stochastic cycling. Trained cyclists (n = 16) were equally divided into 2 groups (MC or isoenergetic placebo (PLA)) and consumed 30 mL of supplement, twice per day for 8 consecutive days. On the fifth day of supplementation, participants completed a 109-min cycling trial designed to replicate road race demands. Functional performance (maximum voluntary isometric contraction (MVIC), cycling efficiency, 6-s peak cycling power) and delayed onset muscle soreness were assessed at baseline, 24, 48, and 72 h post-trial. Blood samples collected at baseline, immediately pre- and post-trial, and at 1, 3, 5, 24, 48, and 72 h post-trial were analysed for indices of inflammation (interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor alpha, high-sensitivity C-reactive protein (hsCRP)), oxidative stress (lipid hydroperoxides), and muscle damage (creatine kinase). MVIC (P < 0.05) did not decline in the MC group (vs. PLA) across the 72-h post-trial period and economy (P < 0.05) was improved in the MC group at 24 h. IL-6 (P < 0.001) and hsCRP (P < 0.05) responses to the trial were attenuated with MC (vs. PLA). No other blood markers were significantly different between MC and PLA groups. The results of the study suggest that Montmorency cherry concentrate can be an efficacious functional food for accelerating recovery and reducing exercise-induced inflammation following strenuous cycling exercise.


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Luciane Angela Nottar Nesello ◽  
Maria Luisa Maes Lima Beleza ◽  
Marihá Mariot ◽  
Luísa Nathália Bolda Mariano ◽  
Priscila de Souza ◽  
...  

This study evaluated the gastroprotective value of the methanol extracts from fruits of Morus nigra L. (black mulberry (MEMN)) and Rubus niveus Thunb (raspberry (MERN)). The total phenolic compounds and flavonoids were measured, as well as the in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenger activity. The gastroprotective effects of the extracts against 60% ethanol/0.3 M HCl were evaluated in mice. After that, the lipid hydroperoxides and reduced glutathione levels at ulcerated tissue were determined. The effects of extracts on H+/K+-ATPase activity were also verified. The extracts exhibited high contents of polyphenols; however, MERN presented 1.5-fold higher levels. The presence of flavonoids also was confirmed. In addition, MEMN (IC50 = 13.74 μg/mL) and MERN (IC50 = 14.97 μg/mL) scavenged DPPH radical. The MEMN reduced the ulcer area only at 300 mg/kg (p.o.) by 64.06%. Interestingly, MERN decreased the ulcer area in a superior potency (ED50 = 20.88 mg/kg), reducing the ulcer area by 81.86% at 300 mg/kg, and increased the gastric mucin levels. The antioxidant effects of extracts were evidenced by reduced lipoperoxides and increased reduction of glutathione amount in the gastric mucosa. However, MEMN or MERN did not change the H+/K+-ATPase activity. These results confirm that M. nigra and R. niveus are berries with a gastroprotective value by strengthening of gastric protective factors.


2008 ◽  
Vol 52 (3) ◽  
pp. 352-359 ◽  
Author(s):  
Nataliya V. Rohr-Udilova ◽  
Klaus Stolze ◽  
Sandra Sagmeister ◽  
Hans Nohl ◽  
Rolf Schulte-Hermann ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Reza Farhoosh

AbstractEffect of hydroxytyrosol (HT) and tert-butylhydroquinone (TBHQ) on the kinetics of lipid hydroperoxides (LOOH) accumulation during the initiation and propagation peroxidations of canola and fish oils at 60 °C was studied. The initiation kinetics of the inhibited peroxidation indicated considerable relative activities, A, for HT and TBHQ in the canola (> 3200 and > 27,000, respectively) and fish (> 120 and > 5000, respectively) oils. The critical concentrations of LOOH reverse micelles (CMCL = 33 mM and 57 mM in the canola and fish, respectively, oils) significantly decreased, on average, to about one-third and 8% of the initial values for HT and TBHQ, respectively. Interestingly, the propagation kinetics of the inhibited peroxidation demonstrated that the antioxidants were still able to inhibit peroxidation, so that the relative propagation oxidizability parameter Rn′ was significantly improved to < 0.5 for HT and to < 0.2 for TBHQ in the canola and fish, respectively, oils.


1987 ◽  
Vol 20 (5) ◽  
pp. 797-807 ◽  
Author(s):  
Kazuaki Akasaka ◽  
Tateo Suzuki ◽  
Hiroshi Ohrui ◽  
Hiroshi Meguro
Keyword(s):  

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