A lipid perspective on regulated cell death

Flores‐Romero, Hector; Ros, Uris; García‐Sáez, Ana J.

doi:10.1016/bs.ircmb.2019.11.004

Cited by 22 publications

(11 citation statements)

References 254 publications

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“…It has been suggested that 5-FU can induce oxidative stress to cause abnormal endoplasmic reticulum function to affect lipid synthesis, inhibit the expression of lipid metabolism genes, and ultimately lead to lipid deposition. Studies have also demonstrated that lipid deposition aggravates the production of ROS, which leads to cell apoptosis (51)(52)(53). In our experiment, we also observed that after 5-FU treatment, the apoptotic cells in the mouse liver increased.…”

Section: Discussionsupporting

confidence: 77%

Angelica Polysaccharide Antagonizes 5-FU-Induced Oxidative Stress Injury to Reduce Apoptosis in the Liver Through Nrf2 Pathway

et al. 2021

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Oxidative stress induced by chemotherapeutic agents causes hepatotoxicity. 5-Fluorouracil (5-FU) has been found to have a variety of side effects, but its toxic effect on the liver and the mechanism are still unclear. Angelica polysaccharide (ASP), the main active ingredient of Dang Gui, has antioxidative stress effects. In this study, we investigated the antagonistic effects of ASP on 5-FU-induced injury in the mouse liver and human normal liver cell line MIHA and the possible mechanism. Our results show that ASP inhibited 5-FU-induced the decrease in Bcl-2 protein and the increase in Bax protein. ASP alleviated 5-FU-induced the increase in alanine aminotransferase (ALT), triglyceride (TG), and aspartate aminotransferase (AST) content; hepatic steatosis; and liver fibrosis. ASP restored 5-FU-induced swelling of mitochondria and the endoplasmic reticulum. 5-FU promoted the expression of Keap1 and increased the binding to NF-E2-related factor 2 (Nrf2) to reduce the nuclear translocation of Nrf2, thereby weakening the transcriptional activity of Nrf2 to inhibit the expression of HO-1; reducing the activity of GSH, SOD, and CAT to increase ROS content; and aggravating DNA damage (indicated by the increase in 8-OHdG). However, ASP reversed these reactions. In conclusion, ASP attenuated the 5-FU-induced Nrf2 pathway barrier to reduce oxidative stress injury and thereby inhibit the disorder of lipid anabolism and apoptosis. The study provides a new protectant for reducing the hepatic toxicity caused by 5-FU and a novel target for treating the liver injury.

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Section: Discussionsupporting

confidence: 77%

Angelica Polysaccharide Antagonizes 5-FU-Induced Oxidative Stress Injury to Reduce Apoptosis in the Liver Through Nrf2 Pathway

et al. 2021

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“…This includes most pore‐forming toxins (PFTs), which are some of the most potent virulence factors found in nature (Ros & Garcia‐Saez, 2015; Dal Peraro & van der Goot, 2016) or perforin, which is released by cytotoxic T cells and Natural Killer cells (Voskoboinik et al , 2015; Prinz et al , 2020). PFPs can also be intracellular executioners as components of cell death signaling pathways (Espiritu et al , 2019; Flores‐Romero et al , 2020). For instance, Bcl‐2‐associated X protein (BAX) and BCL2‐antagonist/killer 1 (BAK) form pores that lead to mitochondrial outer membrane permeabilization (MOMP) during intrinsic apoptosis.…”

Section: Pore Formation In Membranes Is a Conserved Strategy To Kill mentioning

confidence: 99%

Pore formation in regulated cell death

2020

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The discovery of alternative signaling pathways that regulate cell death has revealed multiple strategies for promoting cell death with diverse consequences at the tissue and organism level. Despite the divergence in the molecular components involved, membrane permeabilization is a common theme in the execution of regulated cell death. In apoptosis, the permeabilization of the outer mitochondrial membrane by BAX and BAK releases apoptotic factors that initiate the caspase cascade and is considered the point of no return in cell death commitment. Pyroptosis and necroptosis also require the perforation of the plasma membrane at the execution step, which involves Gasdermins in pyroptosis, and MLKL in the case of necroptosis. Although BAX/BAK, Gasdermins and MLKL share certain molecular features like oligomerization, they form pores in different cellular membranes via distinct mechanisms. Here, we compare and contrast how BAX/BAK, Gasdermins, and MLKL alter membrane permeability from a structural and biophysical perspective and discuss the general principles of membrane permeabilization in the execution of regulated cell death.

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“…[1] i = 0, 1, or 2 for RD0, RD1, RD2 RCSA ~ kCSA wP 2 (kCSA is a constant) [2] In this work, the relevant parameters extracted directly from the data for each NMRD are the dipolar correlation time (tDi) and the maximum relaxation rate (RDi(0)). The addition of RCSA is important for fitting the 31 P data, but not useful otherwise because we cannot estimate a correlation time for this mechanism.…”

Section: Experimental Methodsmentioning

confidence: 99%

“…1 These include motions ascribed to an individual phospholipid such as acyl chain isomerizations (~1 to 10 ps), wobbling of an individual molecule about its long axis (~ 10 ns) and lateral diffusion (0.1 to 10 µs) in the membrane, as well as cooperative motions leading to macroscopic motions (e.g., bilayer undulations or bending). The polar headgroups of phospholipids can provide specific binding sites for peripheral membrane proteins whose transient interactions physically alter membrane properties (e.g., cardiolipin interactions with apoptosis effectors in mitochondria 2 ) or whose enzymatic activity modifies membrane composition (e.g., hydrolysis of specific phosphoinositides by phospholipase C enzymes to generate second messengers 3 ). Defining specific phospholipidprotein interactions is clearly important, but understanding how bilayer dynamics respond to the binding of proteins or other additives is also necessary.…”

Section: Introductionmentioning

confidence: 99%

Phospholipids in motion: High Resolution 31P NMR Field Cycling Studies

Roberts

Cai²,

Sivanandam³

et al. 2021

Preprint

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High resolution field cycling 31P NMR spin-lattice relaxometry, where the sample is excited at high field, shuttled in the magnet bore for low field relaxation, then shuttled back to high field for readout of the residual magnetization, provides data on phospholipid dynamics and structure. In the field range from 11.74 down to 0.003 T three dipolar nuclear magnetic relaxation dispersions (NMRDs) and one due to 31P chemical shift anisotropy contribute to R1 of phospholipids. Extraction of correlation times and maximum relaxation amplitudes for these NMRDs provides (1) lateral diffusion constants for different phospholipids in the same bilayer (illustrated with phospholipase C binding), (2) estimates of how additives alter the motion of the phospholipid about its long axis (looking at cholesterol effects), and (3) an average 31P – 1H angle with respect to the bilayer normal, which reveals that polar head group motion is not restricted on a µs timescale. Although this deals exclusively with phospholipids in small unilamellar vesicles, these same NMRDs can be measured for phospholipids in micelles and nanodiscs, making this technique useful for monitoring lipid behavior in a variety of structures.

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A lipid perspective on regulated cell death

Cited by 22 publications

References 254 publications

Angelica Polysaccharide Antagonizes 5-FU-Induced Oxidative Stress Injury to Reduce Apoptosis in the Liver Through Nrf2 Pathway

Angelica Polysaccharide Antagonizes 5-FU-Induced Oxidative Stress Injury to Reduce Apoptosis in the Liver Through Nrf2 Pathway

Pore formation in regulated cell death

Phospholipids in motion: High Resolution 31P NMR Field Cycling Studies

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