Lipoxygenases in chronic liver diseases: current insights and future perspectives

Heinrich, Lena; Booijink, Richell; Khurana, Amit; Weiskirchen, Ralf; Bansal, Ruchi

doi:10.1016/j.tips.2021.12.001

Cited by 9 publications

(12 citation statements)

References 94 publications

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“…Meanwhile, ALOX12 and ALOX15 also could oxidize LA to synthesize 9 hydroperoxyoctadecadienoic acid (9-HPODE) and 13-HPODE respectively. These PUFA-derived peroxides may further trigger free radical chain reactions of adjacent lipids to propagate lipid peroxidation and amplify membrane damage. − It is of interest to note that these ferroptosis-promoting enzymes all employ iron as their catalytic center, again validating the central catalytic role of iron species in orchestrating the ferroptosis-associated lipid peroxidation process.…”

Section: Brief Description Of Ferroptosismentioning

confidence: 99%

“…In addition to the nonenzymatic peroxidation through ROS attack, PUFAs can also become peroxided through lipoxygenases via canonical lipid oxidation metabolism pathways. Typically, LOX is a dioxygenase containing nonheme iron catalytic centers, which is capable of catalyzing stereospecific peroxidation of PUFAs at 1-cis-pentadiene and 4-cis-pentadiene positions. − There are six major LOX isoforms in human cells, and recent studies have identified that ALOX12 is essential for P53-dependent ferroptosis. Specifically, ALOX12 may catalyze the oxidation of PUFA chains in membrane phospholipids, but its enzymatic activity can be inhibited by SLC7A11 binding.…”

Section: Metabolic Aspects Of Ferroptosis In the Context Of Tumor Cellsmentioning

confidence: 99%

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Ferroptosis Nanomedicine: Clinical Challenges and Opportunities for Modulating Tumor Metabolic and Immunological Landscape

et al. 2023

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Ferroptosis, a type of regulated cell death driven by iron-dependent phospholipid peroxidation, has captured much attention in the field of nanomedicine since it was coined in 2012. Compared with other regulated cell death modes such as apoptosis and pyroptosis, ferroptosis has many distinct features in the molecular mechanisms and cellular morphology, representing a promising strategy for treating cancers that are resistant to conventional therapeutic modalities. Moreover, recent insights collectively reveal that ferroptosis is tightly connected to the maintenance of the tumor immune microenvironment (TIME), suggesting the potential application of ferroptosis therapies for evoking robust antitumor immunity. From a biochemical perspective, ferroptosis is intricately regulated by multiple cellular metabolic pathways, including iron metabolism, lipid metabolism, redox metabolism, etc., highlighting the importance to elucidate the relationship between tumor metabolism and ferroptosis for developing antitumor therapies. In this review, we provide a comprehensive discussion on the current understanding of ferroptosis-inducing mechanisms and thoroughly discuss the relationship between ferroptosis and various metabolic traits of tumors, which offer promising opportunities for direct tumor inhibition through a nanointegrated approach. Extending from the complex impact of ferroptosis on TIME, we also discussed those important considerations in the development of ferroptosis-based immunotherapy, highlighting the challenges and strategies to enhance the ferroptosis-enabled immunostimulatory effects while avoiding potential side effects. We envision that the insights in this study may facilitate the development and translation of ferroptosis-based nanomedicines for tumor treatment.

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Section: Brief Description Of Ferroptosismentioning

confidence: 99%

Section: Metabolic Aspects Of Ferroptosis In the Context Of Tumor Cellsmentioning

confidence: 99%

Ferroptosis Nanomedicine: Clinical Challenges and Opportunities for Modulating Tumor Metabolic and Immunological Landscape

et al. 2023

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“…SIRT1 can stimulate the expression of antioxidant enzymes such as SOD through the deacetylating activation of the β-catenin and forkhead box O proteins [ 162 ]. In turn, β-catenin mediates the expression of genes such as cyclin D1, which is a critical regulator of cell proliferation and survival and myelocytomatosis.…”

Section: Important Regulatory Factors Of Aldmentioning

confidence: 99%

“…For example, exogenous supplementation with GSH or its precursors, N-acetylcysteine and S-adenosyl methionine, increased the GSH level and antioxidant capacity in hepatocytes, thus increasing liver regeneration rate [ 284 , 285 ]. Additionally, lipoxygenases are critical for the oxidation of PUFAs, and lipoxygenase inhibitors may be potent therapies for chronic liver diseases due to their mediation of ethanol-induced lipid peroxidation [ 162 ].…”

Section: Therapeutic Targets In Aldmentioning

confidence: 99%

Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease

Yan

et al. 2023

J Transl Med

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Alcoholism is a widespread and damaging behaviour of people throughout the world. Long-term alcohol consumption has resulted in alcoholic liver disease (ALD) being the leading cause of chronic liver disease. Many metabolic enzymes, including alcohol dehydrogenases such as ADH, CYP2E1, and CATacetaldehyde dehydrogenases ALDHsand nonoxidative metabolizing enzymes such as SULT, UGT, and FAEES, are involved in the metabolism of ethanol, the main component in alcoholic beverages. Ethanol consumption changes the functional or expression profiles of various regulatory factors, such as kinases, transcription factors, and microRNAs. Therefore, the underlying mechanisms of ALD are complex, involving inflammation, mitochondrial damage, endoplasmic reticulum stress, nitrification, and oxidative stress. Moreover, recent evidence has demonstrated that the gut-liver axis plays a critical role in ALD pathogenesis. For example, ethanol damages the intestinal barrier, resulting in the release of endotoxins and alterations in intestinal flora content and bile acid metabolism. However, ALD therapies show low effectiveness. Therefore, this review summarizes ethanol metabolism pathways and highly influential pathogenic mechanisms and regulatory factors involved in ALD pathology with the aim of new therapeutic insights.

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“…Apart from the Fenton reaction, arachidonyl phospholipid and adrenalacyl phospholipid were catalyzed by acyl-CoA synthetase long-chain family member 4 (ACSL4), lysophosphatidylcholine acyltransferase 3 (LPCAT3) and 15-lipoxygenase to produce LPO [46]. LPO attacks PUFAs and expands oxidative reactions under the action of lipoxygenases (LOXs), causing damage [47]. In addition, ACSL4 is a pivotal enzyme in regulating lipid composition and has been shown to contribute to the execution of ferroptosis [48].…”

Section: Iron Metabolismmentioning

confidence: 99%

Ferroptosis as a Potential Therapeutic Target of Traditional Chinese Medicine for Mycotoxicosis: A Review

Ding

Lin

et al. 2023

Toxics

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Mycotoxin contamination has become one of the biggest hidden dangers of food safety, which seriously threatens human health. Understanding the mechanisms by which mycotoxins exert toxicity is key to detoxification. Ferroptosis is an adjustable cell death characterized by iron overload and lipid reactive oxygen species (ROS) accumulation and glutathione (GSH) depletion. More and more studies have shown that ferroptosis is involved in organ damage from mycotoxins exposure, and natural antioxidants can alleviate mycotoxicosis as well as effectively regulate ferroptosis. In recent years, research on the treatment of diseases by Chinese herbal medicine through ferroptosis has attracted more attention. This article reviews the mechanism of ferroptosis, discusses the role of ferroptosis in mycotoxicosis, and summarizes the current status of the regulation of various mycotoxicosis through ferroptosis by Chinese herbal interventions, providing a potential strategy for better involvement of Chinese herbal medicine in the treatment of mycotoxicosis in the future.

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Lipoxygenases in chronic liver diseases: current insights and future perspectives

Cited by 9 publications

References 94 publications

Ferroptosis Nanomedicine: Clinical Challenges and Opportunities for Modulating Tumor Metabolic and Immunological Landscape

Ferroptosis Nanomedicine: Clinical Challenges and Opportunities for Modulating Tumor Metabolic and Immunological Landscape

Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease

Ferroptosis as a Potential Therapeutic Target of Traditional Chinese Medicine for Mycotoxicosis: A Review

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