Involvement of 4-hydroxy-2-nonenal in the pathogenesis of pulmonary fibrosis

Reyes-Jiménez, Edilburga; Ramírez-Hernández, Alma Aurora; Santos-Álvarez, Jovito Cesar; Velázquez-Enríquez, Juan Manuel; Pina-Canseco, Socorro; Baltiérrez-Hoyos, Rafael; Vásquez-Garzón, Verónica Rocío

doi:10.1007/s11010-021-04244-9

Cited by 18 publications

(20 citation statements)

References 114 publications

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“…4-HNE is a highly reactive electrophile and can react with proteins, phospholipids and nucleic acids [ 81 ]. It can covalently modify His, Cys and Lys residues, causing functional impairment of proteins, leading to inhibition of enzyme activity and induction of apoptosis [ 82 , 83 , 84 ]. Thus, 4-HNE can act as a second messenger of free radicals and a growth regulatory factor [ 82 , 83 , 84 ].…”

Section: Post-translational Modifications Of Hsp70 Under Oxidative St...mentioning

confidence: 99%

“…It can covalently modify His, Cys and Lys residues, causing functional impairment of proteins, leading to inhibition of enzyme activity and induction of apoptosis [ 82 , 83 , 84 ]. Thus, 4-HNE can act as a second messenger of free radicals and a growth regulatory factor [ 82 , 83 , 84 ]. The antibiotic plakortin can generate ROS and 4-HNE as products of lipoperoxides [ 85 ].…”

Section: Post-translational Modifications Of Hsp70 Under Oxidative St...mentioning

confidence: 99%

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Hsp70 in Redox Homeostasis

Zhang

Gong

et al. 2022

Cells

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Cellular redox homeostasis is precisely balanced by generation and elimination of reactive oxygen species (ROS). ROS are not only capable of causing oxidation of proteins, lipids and DNA to damage cells but can also act as signaling molecules to modulate transcription factors and epigenetic pathways that determine cell survival and death. Hsp70 proteins are central hubs for proteostasis and are important factors to ameliorate damage from different kinds of stress including oxidative stress. Hsp70 members often participate in different cellular signaling pathways via their clients and cochaperones. ROS can directly cause oxidative cysteine modifications of Hsp70 members to alter their structure and chaperone activity, resulting in changes in the interactions between Hsp70 and their clients or cochaperones, which can then transfer redox signals to Hsp70-related signaling pathways. On the other hand, ROS also activate some redox-related signaling pathways to indirectly modulate Hsp70 activity and expression. Post-translational modifications including phosphorylation together with elevated Hsp70 expression can expand the capacity of Hsp70 to deal with ROS-damaged proteins and support antioxidant enzymes. Knowledge about the response and role of Hsp70 in redox homeostasis will facilitate our understanding of the cellular knock-on effects of inhibitors targeting Hsp70 and the mechanisms of redox-related diseases and aging.

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Section: Post-translational Modifications Of Hsp70 Under Oxidative St...mentioning

confidence: 99%

Section: Post-translational Modifications Of Hsp70 Under Oxidative St...mentioning

confidence: 99%

Hsp70 in Redox Homeostasis

Zhang

Gong

et al. 2022

Cells

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“…OS promotes structural and functional damage to DNA, proteins, and lipids. LPO actively participates in OS-mediated cellular damage and is represented by the overexpression of its by-products, particularly 4-HNE [ 13 ]. Our results of the 4-HNE immunohistochemical analysis show a significant increase in the BLM+CMC group compared to the CT+CMC group, consistent with other studies performed in murine models and samples from patients with lung diseases [ 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

“…ROS interact with biomolecules such as DNA, RNA, proteins, and lipids, and their by-products are used as markers of oxidative damage. In this regard, increased levels of 4-hydroxy-2-nonenal (4-HNE), a marker of oxidative lipid damage, have been observed in IPF lung sample [ 13 , 14 ]. Glutathione (GSH) is a hydrophilic tripeptide that acts as the most critical antioxidant and protects cells against endogenous and exogenous toxicants, such as ROS [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

3′5-Dimaleamylbenzoic Acid Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice

González-García

López-Martínez

Velázquez-Enríquez

et al. 2022

IJMS

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Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by parenchymal scarring, leading progressively to alveolar architecture distortion, respiratory failure, and eventually death. Currently, there is no effective treatment for IPF. Previously, 3′5-dimaleamylbenzoic acid (3′5-DMBA), a maleimide, demonstrated pro-apoptotic, anti-inflammatory, and anti-cancer properties; however, its potential therapeutic effects on IPF have not been addressed. Bleomycin (BLM) 100 U/kg was administered to CD1 mice through an osmotic minipump. After fourteen days of BLM administration, 3′5-DMBA (6 mg/kg or 10 mg/kg) and its vehicle carboxymethylcellulose (CMC) were administered intragastrically every two days until day 26. On day 28, all mice were euthanized. The 3′5-DMBA effect was assessed by histological and immunohistochemical staining, as well as by RT-qPCR. The redox status on lung tissue was evaluated by determining the glutathione content and the GSH/GSSG ratio. 3′5-DMBA treatment re-established typical lung histological features and decreased the expression of BLM-induced fibrotic markers: collagen, α-SMA, and TGF-β1. Furthermore, 3′5-DMBA significantly reduced the expression of genes involved in fibrogenesis. In addition, it decreased reduced glutathione and increased oxidized glutathione content without promoting oxidative damage to lipids, as evidenced by the decrease in the lipid peroxidation marker 4-HNE. Therefore, 3′5-DMBA may be a promising candidate for IPF treatment.

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“…Previously, we and others have reported 3′UTR regulation of profibrotic genes as a result of dysregulation in APA machinery proteins in human diseases like heart failure 1 and chronic obstructive pulmonary disease (COPD) 6 where oxidative stress is prevalent. 2,4 ALDH2 is well known to metabolize and prevent 4HNE accumulation and ROS release, ultimately alleviating oxidative stress, inflammation and fibrosis. Alda-1 is an agonist of ALDH2 which has been shown to increase its enzymatic activity.…”

mentioning

confidence: 99%