Interaction of nonsteroidal anti-inflammatory drugs with membranes: In vitro assessment and relevance for their biological actions

Pereira-Leite, Catarina; Nunes, Cláudia; Reis, Salette

doi:10.1016/j.plipres.2013.08.003

Cited by 96 publications

(88 citation statements)

References 129 publications

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“…However, the content of PA(18:0/18:4) in 24 h under the drug intervention status was lower than that under inflammation status. In previous studies, it was believed that the content decrease and synthesis inhibition of PA type could inhibit the synthesis of NOS and cyclooxygenase as well as the release of TNF-a and enhance the endocytosis, which was an anti-inflammatory effect of macrophages [22,23]. Therefore, the content decrease of PA(18:0/18:4) might be caused by the enhanced endocytosis capacity [24].…”

Section: Discussionmentioning

confidence: 98%

Dynamic analysis of phospholipid metabolism of mouse macrophages treated with common non-steroidal anti-inflammatory drugs

Peng

Zhao

et al. 2015

Mol Cell Biochem

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Through studying the changes of the total phospholipid components in mouse macrophages under the inflammatory status and the drug intervention status, we found the targets of non-steroidal anti-inflammatory drugs on phospholipids, thus providing the basis for the targets of in vitro anti-inflammatory effects of non-steroidal anti-inflammatory drugs. After RAW264.7 cells were pretreated with common non-steroidal anti-inflammatory drugs (aspirin and ibuprofen) and, respectively, stimulated with KLA for various periods (0.5, 4, 12, 16, and 24 h), the phospholipids were extracted. The dynamic changes of phospholipids in cells under various stimulations were analyzed with UPLC-Q-TOF-MS technique. Through the statistical analysis of Simca-P, we explored the potential targets of non-steroidal anti-inflammatory drugs on phospholipids. Through the dynamic analysis of phospholipids, we found two biomarkers (PC(17:1/18:1), PA(18:0/18:4)) which might be in vitro intervention inflammatory response targets of non-steroidal anti-inflammatory drugs. The analysis results show that in anti-inflammatory effects, non-steroidal anti-inflammatory drugs can inhibit COX, induce the cellular fatty acid desaturation and the changes of phospholipid components, stimulate free fatty acids, activate calcium ion channels of endoplasmic reticulum, and promote cell endocytosis, thus controlling inflammation and activating cells. Non-steroidal anti-inflammatory drugs can promote endocytosis, alter cell inflammatory response, and activate the process cells, thus realizing the anti-inflammatory effects.

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Section: Discussionmentioning

confidence: 98%

Dynamic analysis of phospholipid metabolism of mouse macrophages treated with common non-steroidal anti-inflammatory drugs

Peng

Zhao

et al. 2015

Mol Cell Biochem

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“…In particular, non-steroidal anti-inflammatory drugs (NSAID's) have been shown to disturb bilayer structures in native and model membranes 68,69 . Aspirin is the most common NSAID and is known to interact with membranes 15,68 .…”

Section: Discussionmentioning

confidence: 99%

The Molecular Structure of Human Red Blood Cell Membranes From Highly Oriented, Solid Supported Multi-Lamellar Membranes

Himbert

Alsop

Rheinstädter

2018

Biophysical Journal

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We prepared highly oriented, multi-lamellar stacks of human red blood cell (RBC) membranes applied on silicon wafers. RBC ghosts were prepared by hemolysis and applied onto functionalized silicon chips and annealed into multi-lamellar RBC membranes. High resolution X-ray diffraction was used to determine the molecular structure of the stacked membranes. We present direct experimental evidence that these RBC membranes consist of nanometer sized domains of integral coiled-coil peptides, as well as liquid ordered (l o ) and liquid disordered (l d ) lipids. Lamellar spacings, membrane and hydration water layer thicknesses, areas per lipid tail and domain sizes were determined. The common drug aspirin was added to the RBC membranes and found to interact with RBC membranes and preferably partition in the head group region of the l o domain leading to a fluidification of the membranes, i.e., a thinning of the bilayers and an increase in lipid tail spacing. Our results further support current models of RBC membranes as patchy structures and provide unprecedented structural details of the molecular organization in the different domains.The presence of pale cells with no internal content in a blood smear is typically indicative of a disease. These cells are produced by hemolysis and have been named red blood cell (RBC) ghosts based on their appearance under the microscope. RBC ghosts can be prepared artificially [1][2][3] . The first published protocol in 1963 by Dodge, Mitchell and Hanahan describes the extraction of the cell membrane from RBCs through hemolysis and was an essential step in the development of membrane proteomics and lipidomics 4,5 . While there is detailed knowledge of the composition of RBC membranes, information about the molecular organization of these components in the actual membranes is scarce 6 . This is, in particular, a consequence of the lack of suitable experimental techniques. The disordered, patchy and highly dynamic state of biological materials impedes, for instance, the use of high-resolution diffraction techniques as in protein crystallography. To overcome this constraint, we prepared highly oriented stacks of RBC membranes on silicon wafers and studied their molecular properties in-vitro using high resolution X-ray diffraction. The results present evidence for nanometer-sized domains of coiled-coils peptides, as well as liquid ordered (l o ) and liquid disordered (l d ) lipid patches, and give a detailed picture of the molecular organization in these domains.When present in the body, aspirin (acetylsalicylic acid, ASA) and its metabolites interact with the cyclo-oxygenase (COX) pathway. The inhibition of both COX isoforms, COX-1 and COX-2, by higher dose aspirin is believed to lead to analgesic and anti-inflammatory effects, while lower doses, sufficient to inhibit COX-1 activity, lead to anti-platelet activity 7,8 . There is recent evidence that membrane composition and fluidity play an important role in platelet cell function [9][10][11] , possibly related to the formation of rafts 12 .

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“…In a proposed mechanism for NSAID induced apoptosis, NSAIDs would promote cell membrane permeabilization, due to their ability to interact with membranes and cause alterations in hydrophobicity, fluidity, biochemical properties, and stability (reviewed in [44]). Higher permeability would stimulate calcium influx, leading to increased calcium levels in the cytoplasm, which then could culminate in ER stress.…”

Section: Er Stress In Nsaids-induced Effects Of Cytotoxicitymentioning

confidence: 99%

Endoplasmic reticulum stress response in the roadway for the effects of non-steroidal anti-inflammatory drugs

Mügge

Silva

2015

Endoplasmic Reticulum Stress in Diseases

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Over the past decade, a handful of evidence has been provided that nonsteroidal anti-inflammatory drugs (NSAIDs) display effects on the homeostasis of the endoplasmic reticulum (ER). Their uptake into cells will eventually lead to activation or inhibition of key molecules that mediate ER stress responses, raising not only a growing interest for a pharmacological target in ER stress responses but also important questions how the ER-stress mediated effects induced by NSAIDs could be therapeutically advantageous or not. We review here the toxicity effects and therapeutic applications of NSAIDs involving the three majors ER stress arms namely PERK, IRE1, and ATF6. First, we provide brief introduction on the well-established and characterized downstream events mediated by these ER stress players, followed by presentation of the NSAIDs compounds and mode of action, and finally their effects on ER stress response. NSAIDs present promising drug agents targeting the components of ER stress in different aspects of cancer and other diseases, but a better comprehension of the mechanisms underlying their benefits and harms will certainly pave the road for several diseases’ therapy.

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Interaction of nonsteroidal anti-inflammatory drugs with membranes: In vitro assessment and relevance for their biological actions

Cited by 96 publications

References 129 publications

Dynamic analysis of phospholipid metabolism of mouse macrophages treated with common non-steroidal anti-inflammatory drugs

Dynamic analysis of phospholipid metabolism of mouse macrophages treated with common non-steroidal anti-inflammatory drugs

The Molecular Structure of Human Red Blood Cell Membranes From Highly Oriented, Solid Supported Multi-Lamellar Membranes

Endoplasmic reticulum stress response in the roadway for the effects of non-steroidal anti-inflammatory drugs

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