Malondialdehyde-Acetaldehyde Extracellular Matrix Protein Adducts Attenuate Unfolded Protein Response During Alcohol and Smoking–Induced Pancreatitis

Bhatia, Rakesh; Thompson, Christopher; Clement, Emalie J.; Ganguly, Koelina; Cox, Jesse L.; Rauth, Sanchita; Siddiqui, Jawed A.; Mashiana, Simran S; Jain, Maneesh; Wyatt, Todd A.; Mashiana, Harmeet S.; Singh, Shailender; Woods, Nicholas T.; Kharbanda, Kusum K.; Batra, Surinder K.; Kumar, Sushil

doi:10.1053/j.gastro.2022.06.071

Cited by 13 publications

(7 citation statements)

References 49 publications

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“…11 In a 2017 study, Lugea et al 12 demonstrated that cigarette smoke together with alcohol contribute to CP pathogenesis through endoplasmic reticulum (ER) stress in pancreatic acinar cells. In this issue, findings of Bhatia et al 13 provide an even closer mechanistic link between chronic ethanol and smoke exposure and ER stress-induced pancreatitis.…”

mentioning

confidence: 85%

“…To tackle this knowledge gap, in the present study, Bhatia et al 13 performed proteomic analysis on a mouse model of secretagogue-induced RAP/CP with chronic alcohol and cigarette smoke extract exposure. They identified stable malondialdehyde-acetaldehyde adducts on the deposited extracellular matrix proteins in the pancreas of mice with RAP/CP and in pancreatic samples from patients with CP.…”

mentioning

confidence: 99%

“…Thus, therapeutic interventions should aim at the prevention of pancreatic damage and specifically inhibit pathways activated by the pancreatitis-causing toxic substances. In this regard, the discovery of Bhatia et al13 identifies malondialdehyde-acetaldehyde adducts as novel therapeutic targets in the prevention and treatment of pancreatitis associated with alcohol abuse and smoking.…”

mentioning

confidence: 99%

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Aldehyde “Adduction” Explains Synergy of Smoking and Alcohol in Promoting Pancreatitis

Geisz

2022

Gastroenterology

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confidence: 85%

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confidence: 99%

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confidence: 99%

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Aldehyde “Adduction” Explains Synergy of Smoking and Alcohol in Promoting Pancreatitis

Geisz

2022

Gastroenterology

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“…Moreover, MDA can react with amino acids and yield different adducts such as MDA-lysine [ 40 ], and MDA-glycine [ 70 ]. Moreover, the MDA-acetaldehyde protein adduct termed malondialdehyde–acetaldehyde (MAA) has been reported to have a role in several diseases, like pancreatitis [ 71 ], atherosclerosis [ 72 ], RA [ 73 ], and inflammatory bowel disease [ 74 ]. Following, we will discuss the role of lipid peroxidation-derived 4-HNE and MDA in the development of OA.…”

Section: Pathological Aspects Of Lipid Peroxidation In Oamentioning

confidence: 99%

Lipid peroxidation in osteoarthritis: focusing on 4-hydroxynonenal, malondialdehyde, and ferroptosis

Zhang,

Hou,

Guo

et al. 2023

Cell Death Discov.

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Osteoarthritis (OA) is a multifactorial and increasingly prevalent degenerative disease that affects the whole joint. The pathogenesis of OA is poorly understood and there is a lack of therapeutic interventions to reverse the pathological process of this disease. Accumulating studies have shown that the overproduction of reactive oxygen species (ROS) and ROS-induced lipid peroxidation are involved in the pathogenesis of OA. 4-Hydroxy-2-nonenal (4-HNE) and malondialdehyde (MDA) have received considerable attention for their role in cartilage degeneration and subchondral bone remodeling during OA development. Ferroptosis is a form of cell death characterized by a lack of control of membrane lipid peroxidation and recent studies have suggested that chondrocyte ferroptosis contributes to OA progression. In this review, we aim to discuss lipid peroxidation-derived 4-HNE and MDA in the progression of OA. In addition, the therapeutic potential for OA by controlling the accumulation of lipid peroxidation and inhibiting chondrocyte ferroptosis are discussed.

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“…[10][11][12] One prominent component found in tobacco, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, exacerbates the damage to acinar cells by binding to nicotine acetylcholine receptors. [13] Additionally, a recent study [14] demonstrated that exposure to combined alcohol and tobacco in mice resulted in the formation of malondialdehydeacetaldehyde (MAA) adducts in the pancreatic extracellular matrix (ECM) proteins. This adduct formation inhibited the unfolded protein response of acinar cells, induced ER stress, and impeded acinar cell regeneration.…”

Section: Environmental Factorsmentioning

confidence: 99%

A comprehensive review of recent advances in chronic pancreatitis

Mao,

Zou,

Mao

et al. 2023

Journal of Pancreatology

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Chronic pancreatitis (CP) is a multifaceted disorder influenced by environmental and genetic factors, with smoking and alcohol consumption being major contributors. Recent developments encompass the advent of innovative transgenic models and the identification of susceptibility genes, shedding light on the genetic aspect of CP. The pathogenesis of this disease involves a complex interplay of pancreatic acinar cell dysfunction, inflammatory reactions, and fibrosis. Current research delves into understanding these molecular mechanisms. Pain, a pivotal symptom of CP, has been increasingly studied to develop effective therapeutic interventions. Diagnostic advancements, including endoscopic ultrasound, radiomics, and blood-based markers, have shown potential in enhancing early CP detection. Moreover, recent clinical trials have optimized treatment approaches, such as pancreatic stone fragmentation, stent placement, and decision-making between endoscopic and surgical procedures. Emerging therapies, including chemical pancreatectomy and gene therapy, present promising opportunities for improved CP management.

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Malondialdehyde-Acetaldehyde Extracellular Matrix Protein Adducts Attenuate Unfolded Protein Response During Alcohol and Smoking–Induced Pancreatitis

Cited by 13 publications

References 49 publications

Aldehyde “Adduction” Explains Synergy of Smoking and Alcohol in Promoting Pancreatitis

Aldehyde “Adduction” Explains Synergy of Smoking and Alcohol in Promoting Pancreatitis

Lipid peroxidation in osteoarthritis: focusing on 4-hydroxynonenal, malondialdehyde, and ferroptosis

A comprehensive review of recent advances in chronic pancreatitis

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