scholarly journals Photolysis of incorporated benzophenone derivatives inside compressed lipid monolayers

2001 ◽  
Vol 66 (5) ◽  
pp. 309-322 ◽  
Author(s):  
Dejan Markovic
Keyword(s):  
Lipid Peroxidation ◽  
Lipid Peroxides ◽  
Lipid Monolayers ◽  
Cage Effect ◽  
Chain Mechanism ◽  
Hydrogen Atoms ◽  
Chain Reaction ◽  
Radical Type ◽  
Lipid Radicals

The goal of this work was to study the possibility of the occurrence of radical- type lipid peroxidation of the lipid constituents on biomembranes, in compressed monolayers, having lipoidal benzophenone photosensitizers incorporated. The triplets of the photosensitizer abstract allylic and doubly-allylic hydrogen atoms from anticonjugated moities of the lipid molecules. The results simultaneously confirmed the occurrence of H-abstraction (and so the initiation of the peroxidizing chain mechanism), and the absence of the formation of lipid peroxides. The reason lies in "cage effect": the highly restricted spacial area of compressed lipid monolayers limits the mobility of the created radicals (lipid radicals and ketyl radicals) and leads to their recombination, thus preventing the propagation step of the chain mechanism. With certain reservations it may be concluded that these results have a clear implication on real biomembranes: the structure of which is one of themain factors preventing the spread of the chain reaction, and the formation of lipid peroxides.

Benzophenone-Sensitized Peroxidation in Compressed Lipid Monolayers at Air-Water Interface

2001 ◽  
Vol 66 (11) ◽  
pp. 1603-1614 ◽  
Author(s):  
Dejan Z. Markovic
Keyword(s):  
Lipid Peroxide ◽  
Lipid Monolayers ◽  
Chain Mechanism ◽  
Hydrogen Atoms ◽  
Peroxide Formation ◽  
Chain Reaction ◽  
Air Water Interface ◽  
Main Factors ◽  
Radical Type ◽  
Lipid Peroxide Formation

The paper reports on a study of radical-type lipid peroxidation of biomembrane lipid constituents in compressed monolayers, with incorporated lipoidic benzophenone photosensitizers. Their triplets abstract allylic and double-allylic hydrogen atoms from hydrophobic moieties of the lipid molecules. The results confirmed the H abstraction occurrence (and thus the initiation of the peroxidizing chain mechanism), and absence of lipid peroxide formation at the same time. The reason is in the "cage effect": highly restricted spatial area of compressed lipid monolayers limits mobility of the formed radicals (lipid and ketyl radicals) and leads to their recombination, preventing the propagation step of the chain mechanism. With certain approximation, one may conclude that these results have clear implication for real biomembranes: their structure is one of the main factors in prevention of spreading of the chain reaction, and lipid peroxide formation.

scholarly journals The mechanism of Fe2+-initiated lipid peroxidation in liposomes: the dual function of ferrous ions, the roles of the pre-existing lipid peroxides and the lipid peroxyl radical

2000 ◽  
Vol 352 (1) ◽  
pp. 27-36 ◽  
Author(s):  
Lixia TANG ◽  
Yong ZHANG ◽  
Zhongming QIAN ◽  
Xun SHEN
Keyword(s):  
Lipid Peroxidation ◽  
Latent Period ◽  
Time Lag ◽  
Lipid Peroxides ◽  
Peroxyl Radicals ◽  
Dual Function ◽  
Critical Ratio ◽  
Ferrous Ions ◽  
Liposomal System ◽  
Lipid Peroxyl Radicals

The mechanism of Fe2+-initiated lipid peroxidation in a liposomal system was studied. It was found that a second addition of ferrous ions within the latent period lengthened the time lag before lipid peroxidation started. The apparent time lag depended on the total dose of Fe2+ whenever the second dose of Fe2+ was added, which indicates that Fe2+ has a dual function: to initiate lipid peroxidation on one hand and suppress the species responsible for the initiation of the peroxidation on the other. When the pre-existing lipid peroxides (LOOH) were removed by incorporating triphenylphosphine into liposomes, Fe2+ could no longer initiate lipid peroxidation and the acceleration of Fe2+ oxidation by the liposomes disappeared. However, when extra LOOH were introduced into liposomes, both enhancement of the lipid peroxidation and shortening of the latent period were observed. When the scavenger of lipid peroxyl radicals (LOOP), N,N´-diphenyl-p-phenylene-diamine, was incorporated into liposomes, neither initiation of the lipid peroxidation nor acceleration of the Fe2+ oxidation could be detected. The results may suggest that both the pre-existing LOOH and LOOP are necessary for the initiation of lipid peroxidation. The latter comes initially from the decomposition of the pre-existing LOOH by Fe2+ and can be scavenged by its reaction with Fe2+. Only when Fe2+ is oxidized to such a degree that LOOP is no longer effectively suppressed does lipid peroxidation start. It seems that by taking the reactions of Fe2+ with LOOH and LOOP into account, the basic chemistry in lipid peroxidation can explain fairly well the controversial phenomena observed in Fe2+-initiated lipid peroxidation, such as the existence of a latent period, the critical ratio of Fe2+ to lipid and the required oxidation of Fe2+.

scholarly journals APR-246 induces early cell death by ferroptosis in acute myeloid leukemia.

Haematologica ◽  
2021 ◽  
Author(s):  
Rudy Birsen ◽  
Clement Larrue ◽  
Justine Decroocq ◽  
Natacha Johnson ◽  
Nathan Guiraud ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Cell Death ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Ex Vivo ◽  
Lipid Peroxides ◽  
Death Process ◽  
Glutathione Biosynthesis ◽  
Acute Myeloid

APR-246 is a promising new therapeutic agent that targets p53 mutated proteins in myelodysplastic syndromes and in acute myeloid leukemia. APR-246 reactivates the transcriptional activity of p53 mutants by facilitating their binding to DNA target sites. Recent studies in solid cancers have found that APR-246 can also induce p53-independent cell death. In this study, we demonstrate that AML cell death occurring early after APR-246 exposure is suppressed by iron chelators, lipophilic antioxidants and inhibitors of lipid peroxidation, and correlates with the accumulation of markers of lipid peroxidation, thus fulfilling the definition of ferroptosis, a recently described cell death process. The capacity of AML cells to detoxify lipid peroxides by increasing their cystine uptake to maintain major antioxidant molecule glutathione biosynthesis after exposure to APR-246 may be a key determinant of sensitivity to this compound. The association of APR-246 with induction of ferroptosis (either by pharmacological compounds, or genetic inactivation of SLC7A11 or GPX4) had a synergistic effect on the promotion of cell death, both in vivo and ex vivo.

Prevention of lipid peroxidation does not prevent oxidant-induced myocardial contractile dysfunction

1994 ◽  
Vol 267 (6) ◽  
pp. H2371-H2377 ◽  
Author(s):  
Y. Kong ◽  
E. J. Lesnefsky ◽  
J. Ye ◽  
L. D. Horwitz
Keyword(s):  
Lipid Peroxidation ◽  
Coronary Flow ◽  
Systolic Function ◽  
Lipid Peroxide ◽  
Left Ventricular Pressure ◽  
Lipid Peroxides ◽  
Left Ventricular ◽  
Contractile Dysfunction ◽  
Myocardial Contractile ◽  
Generating System

We tested whether, with exposure to an extraneous iron-catalyzed free radical-generating system, prevention of lipid peroxidation with U74006F, a 21-aminosteroid, could also prevent myocardial contractile dysfunction. Rabbits received either U74006F (10 mg/kg iv) or vehicle (V). Thirty minutes later the hearts were excised and perfused by a non-recirculating Langendorff technique. Six U74006F- and six V-treated hearts were exposed for 7.5 min to a .OH-generating system (H2O2 and Fe(2+)-ADP chelate). Myocardial lipid peroxides were measured by glutathione peroxidase-catalyzed oxidation of exogenous glutathione. With exposure to .OH, cytosolic lipid peroxide levels were increased threefold in V-treated hearts, but there was no increase in U74006F-treated hearts. After 30 min of recovery, developed pressure and maximum first derivative of left ventricular pressure were greater in U74006F-treated hearts than in V-treated hearts but were still 50 and 44% of levels in saline hearts, respectively. Coronary flow was markedly reduced after exposure to free radicals and was only slightly less depressed when U74006F was administered. When coronary flow following oxidant exposure was increased by nitroglycerin, U74006F again only modestly improved systolic function. Thus, although U74006F blocked lipid peroxidation, it only slightly improved the ventricular dysfunction caused by .OH. Therefore, factors other than lipid peroxidation play a major role in oxidant-induced myocardial stunning.

scholarly journals The α6β4 integrin promotes resistance to ferroptosis

2017 ◽  
Vol 216 (12) ◽  
pp. 4287-4297 ◽  
Author(s):  
Caitlin W. Brown ◽  
John J. Amante ◽  
Hira Lal Goel ◽  
Arthur M. Mercurio
Keyword(s):  
Lipid Peroxidation ◽  
Fatty Acids ◽  
Extracellular Matrix ◽  
Cancer Biology ◽  
Membrane Lipids ◽  
Lipid Peroxides ◽  
Causal Link ◽  
Carcinoma Cells ◽  
Adherent Cells ◽  
Α6β4 Integrin

Increases in lipid peroxidation can cause ferroptosis, a form of cell death triggered by inhibition of glutathione peroxidase 4 (GPX4), which catalyzes the reduction of lipid peroxides and is a target of ferroptosis inducers, such as erastin. The α6β4 integrin protects adherent epithelial and carcinoma cells from ferroptosis induced by erastin. In addition, extracellular matrix (ECM) detachment is a physiologic trigger of ferroptosis, which is evaded by α6β4. The mechanism that enables α6β4 to evade ferroptosis involves its ability to protect changes in membrane lipids that are proferroptotic. Specifically, α6β4-mediated activation of Src and STAT3 suppresses expression of ACSL4, an enzyme that enriches membranes with long polyunsaturated fatty acids and is required for ferroptosis. Adherent cells lacking α6β4 require an inducer, such as erastin, to undergo ferroptosis because they sustain GPX4 expression, despite their increase in ACSL4. In contrast, ECM detachment of cells lacking α6β4 is sufficient to trigger ferroptosis because GPX4 is suppressed. This causal link between α6β4 and ferroptosis has implications for cancer biology and therapy.

Changes in lipid peroxidation and free radical scavengers in the brain of hyper- and hypothyroid aged rats

1995 ◽  
Vol 147 (2) ◽  
pp. 361-365 ◽  
Author(s):  
T Mano ◽  
R Sinohara ◽  
Y Sawai ◽  
N Oda ◽  
Y Nishida ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Free Radical ◽  
Lipid Peroxide ◽  
Lipid Peroxides ◽  
Thiobarbituric Acid ◽  
Free Radical Scavengers ◽  
Aged Rats ◽  
Radical Scavengers ◽  
Old Rats ◽  
The Brain

Abstract To determine how lipid peroxides and free radical scavengers are changed in the brain of hyper- or hypothyroid rats, we examined the behavior of lipid peroxide and free radical scavengers in the cerebral cortex of aged (1·5 years old) rats that had been made hyper- or hypothyroid by the administration of thyroxine or methimazol for 4 weeks. Concentrations of catalase, Mn-superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were increased in hyperthyroid rats compared with euthyroid rats. Concentrations of total SOD, Cu,Zn-SOD and GSH-PX were increased but that of Mn-SOD was decreased in hypothyroid animals. There were no differences among hyperthyroid, hypothyroid and euthyroid rats in the levels of coenzymes 9 or 10. The concentration of lipid peroxides, determined indirectly by the measurement of thiobarbituric acid reactants, was decreased in hyperthyroid rats but not in hypothyroid rats when compared with euthyroid animals. These findings suggest that free radicals and lipid peroxides are scavenged to compensate for the changes induced by hyper- or hypothyroidism. Journal of Endocrinology (1995) 147, 361–365

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