Dissemination of Peroxidative Stress via Intermembrane Transfer of Lipid Hydroperoxides: Model Studies with Cholesterol Hydroperoxides

Vila, Andrew; Korytowski, Witold; Girotti, Albert W.

doi:10.1006/abbi.2000.1928

Cited by 36 publications

(80 citation statements)

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“…Interestingly, 4-hydroxynonenal (4-HNE), an end product of lipid peroxidation that quickly forms adducts with proteins, has been shown to participate in the activation of both processes in other cellular systems. [53][54][55] Different studies have shown that PhLOOHs can translocate/ transfer between membranes, 26,[56][57][58][59] through the cellular aqueous compartments, to expand their signaling oxidative range throughout the cell, at locations remote from the initial site of photo-oxidation. The occurrence of these events is consistent with the generation of long-lived species such as hydroperoxides, including H 2 O 2 .…”

Section: Discussionmentioning

confidence: 99%

Spatiotemporal autophagic degradation of oxidatively damaged organelles after photodynamic stress is amplified by mitochondrial reactive oxygen species

et al. 2012

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Although reactive oxygen species (ROS) have been reported to evoke different autophagic pathways, how ROS or their secondary products modulate the selective clearance of oxidatively damaged organelles is less explored. To investigate the signaling role of ROS and the impact of their compartmentalization in autophagy pathways, we used murine fibrosarcoma L929 cells overexpressing different antioxidant enzymes targeted to the cytosol or mitochondria and subjected them to photodynamic (PD) stress with the endoplasmic reticulum (ER)-associated photosensitizer hypericin. We show that following apical ROS-mediated damage to the ER, predominantly cells overexpressing mitochondria-associated glutathione peroxidase 4 (GPX4) and manganese superoxide dismutase (SOD2) displayed attenuated kinetics of autophagosome formation and overall cell death, as detected by computerized time-lapse microscopy. Consistent with a primary ER photodamage, kinetics and colocalization studies revealed that photogenerated ROS induced an initial reticulophagy, followed by morphological changes in the mitochondrial network that preceded clearance of mitochondria by mitophagy. Overexpression of cytosolic and mitochondria-associated GPX4 retained the tubular mitochondrial network in response to PD stress and concomitantly blocked the progression toward mitophagy. Preventing the formation of phospholipid hydroperoxides and H2O2 in the cytosol as well as in the mitochondria significantly reduced cardiolipin peroxidation and apoptosis. All together, these results show that in response to apical ER photodamage ROS propagate to mitochondria, which in turn amplify ROS production, thereby contributing to two antagonizing processes, mitophagy and apoptosis

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Section: Discussionmentioning

confidence: 99%

Spatiotemporal autophagic degradation of oxidatively damaged organelles after photodynamic stress is amplified by mitochondrial reactive oxygen species

et al. 2012

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“…The transfer activities of recombinant SCP-2 and bSCP-2 were determined by measuring the kinetics of [ 14 C]cholesterol translocation from small unilamellar vesicles (50 nm SUVs) to red cell ghost membranes [14,27,28]. Departure from SUV donors is the rate limiting step in the transfer process [27].…”

Section: Transfer Assaymentioning

confidence: 99%

“…Departure from SUV donors is the rate limiting step in the transfer process [27]. Stock SUVs consisting of 1.0 mM egg PC, 0.8 mM [ 14 C]cholesterol (~1 μCi/ml), and 0.02 mM DCP in bulk suspension were prepared by lipid extrusion, as described [27,28].…”

Section: Transfer Assaymentioning

confidence: 99%

“…Stock SUVs consisting of 1.0 mM egg PC, 0.8 mM [ 14 C]cholesterol (~1 μCi/ml), and 0.02 mM DCP in bulk suspension were prepared by lipid extrusion, as described [27,28]. Unsealed ghosts were prepared by hypotonic lysis of human erythrocytes [27]. Assay mixtures (2.0 ml starting volume) typically contained 0.6 mM total ghost lipid, 0.06 mM total SUV lipid, and 5-10 μM SCP-2 or bSCP-2 in PBS/0.1 mM EDTA/0.1 mM DFO (pH 7.4).…”

Section: Transfer Assaymentioning

confidence: 99%

“…Assay mixtures (2.0 ml starting volume) typically contained 0.6 mM total ghost lipid, 0.06 mM total SUV lipid, and 5-10 μM SCP-2 or bSCP-2 in PBS/0.1 mM EDTA/0.1 mM DFO (pH 7.4). The chelators were included to minimize any metal ion-catalyzed lipid or protein oxidation [14,27,28]. At various times during transfer incubation at 37 °C, a 0.1 ml sample was removed, mixed with ice-cold PBS/EDTA/DFO, and centrifuged (16000 × g, 10 min), after which 0.1 ml of the SUV-containing supernatant was analyzed by scintillation counting.…”

Section: Transfer Assaymentioning

confidence: 99%

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Lipid transfer protein binding of unmodified natural lipids as assessed by surface plasmon resonance methodology

Kernstock

Girotti

2007

Analytical Biochemistry

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A new approach for analyzing lipid-lipid transfer protein interactions is described. The transfer protein is genetically engineered for expression with a C-terminal biotinylated peptide extension (AviTag ® ). This allows protein anchoring to a streptavidin-coated chip for surface plasmon resonance (SPR)-based assessment of lipid binding. Sterol carrier protein-2 (SCP-2), involved in the intracellular trafficking of cholesterol, fatty acids and other lipids, was selected as the prototype. Biotinylated SCP-2 (bSCP-2) was expressed in E. coli, purified to homogeneity by mutated streptavidin (SoftLink ® ) affinity chromatography, and confirmed by mass spectrometry to contain one biotin group at the expected position. Intermembrane [ 14 C]cholesterol transfer was strongly enhanced by bSCP-2, demonstrating that it was functional. Using bSCP-2 immobilized on a Biacore streptavidin chip, we determined on-and off-rate constants along with equilibrium dissociation constants for the following analytes: oleic acid, linoleic acid, cholesterol, and fluorophore (NBD)-derivatized cholesterol. The dissociation constant for NBD-cholesterol was similar to that determined by fluorescence titration for SCP-2 in solution, thus validating the SPR approach. This method can be readily adapted to other transfer proteins and has several advantages over existing techniques for measuring lipid binding, including (i) ability to study lipids in their natural states, i.e. without relatively large reporter groups; and (ii) ability to measure on-and off-rate constants as well as equilibrium constants.

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Generation and Reactivity of Lipid Hydroperoxides in Biological Systems

Girotti

Korytowski

2013

Patai's Chemistry of Functional Groups

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Numerous reviews have been published about the structural/functional damage caused by peroxidation of unsaturated lipids (phospholipids, glycolipids, cholesterol) in model membranes, cellular membranes, and lipoproteins. Less attention has been given to hydroperoxide species (LOOHs), which arise as intermediates of free radical‐mediated (chain) peroxidation or by direct ene‐addition of singlet molecular oxygen. This chapter focuses on nonenzymatic LOOH formation and on LOOH reactivity in biological systems, including cell membranes and lipoproteins. Specialized techniques for analyzing these processes are described. Two competing LOOH reaction pathways are discussed in detail: (i) iron‐catalyzed one‐electron reduction to oxyl radicals (LO • ), which expand chain peroxidation, and (ii) enzyme‐catalyzed two‐electron reduction to alcohols (LOH), which inhibits further chain propagation. In addition to these competing fates, LOOHs can undergo spontaneous or protein‐assisted translocation between membranes, lipoproteins, and membranes and lipoproteins, a more recently recognized phenomenon. Intracellular LOOH transfer could result in damage/toxicity enhancement or abatement, depending on prooxidant vs. antioxidant availability. We also discuss a novel, but still poorly understood response to LOOH trafficking, namely, activation of redox signaling pathways. We postulate that LOOHs, unlike the better known signaling molecule, H 2 O 2 , will be targeted to relatively hydrophobic “sensor” sites and that these sites are distinct from those targeted by H 2 O 2 . Thus, the authors' intent in preparing this chapter was to discuss not only the well‐established chemistry of LOOH generation and turnover, but also LOOH involvement in signal transduction, the importance of which in the field of redox signaling is only beginning to be appreciated.

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Dissemination of Peroxidative Stress via Intermembrane Transfer of Lipid Hydroperoxides: Model Studies with Cholesterol Hydroperoxides

Cited by 36 publications

References 44 publications

Spatiotemporal autophagic degradation of oxidatively damaged organelles after photodynamic stress is amplified by mitochondrial reactive oxygen species

Spatiotemporal autophagic degradation of oxidatively damaged organelles after photodynamic stress is amplified by mitochondrial reactive oxygen species

Lipid transfer protein binding of unmodified natural lipids as assessed by surface plasmon resonance methodology

Generation and Reactivity of Lipid Hydroperoxides in Biological Systems

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