Nicotinamide adenine dinucleotide phosphate oxidase in pancreatic diseases: Mechanisms and future perspectives

Abstract

Pancreatitis and pancreatic cancer (PC) stand as the most worrisome ailments affecting the pancreas. Researchers have dedicated efforts to unraveling the mechanisms underlying these diseases, yet their true nature continues to elude their grasp. Within this realm, oxidative stress is often believed to play a causal and contributory role in the development of pancreatitis and PC. Excessive accumulation of reactive oxygen species (ROS) can cause oxidative stress, and the key enzyme responsible for inducing ROS production in cells is nicotinamide adenine dinucleotide phosphate hydrogen oxides (NOX). NOX contribute to pancreatic fibrosis and inflammation by generating ROS that injure acinar cells, activate pancreatic stellate cells, and mediate macrophage polarization. Excessive ROS production occurs during malignant transformation and pancreatic carcinogenesis, creating an oxidative microenvironment that can cause abnormal apoptosis, epithelial to mesenchymal transition and genomic instability. Therefore, understanding the role of NOX in pancreatic diseases contributes to a more in-depth exploration of the exact pathogenesis of these diseases. In this review, we aim to summarize the potential roles of NOX and its mechanism in pancreatic disorders, aiming to provide novel insights into understanding the mechanisms underlying these diseases.

Keywords: Mechanism; Nicotinamide adenine dinucleotide phosphate hydrogen oxides; Pancreatic cancer; Pancreatitis; Reactive oxygen species.

Figure 1

The scheme of the potential roles of nicotinamide adenine dinucleotide phosphate hydrogen oxides in pancreatic acinar cells and macrophages, which leading the development of acute pancreatitis. NOX: Nicotinamide adenine dinucleotide phosphate hydrogen oxides; AIF: Apoptosis inducing factor; ROS: Reactive oxygen species; NF-κB: Nuclear factor kappa-B; IL: Interleukin; TGF: Transforming growth factor; PDGF: Platelet-derived growth factor; PSC: Pancreatic stellate cell; DPI: Diphenylene iodium.

Figure 2

The scheme of the potential roles of nicotinamide adenine dinucleotide phosphate hydrogen oxides in pancreatic stellate cells and macrophages, which facilitating pancreatic fibrosis of chronic pancreatitis. NOX: Nicotinamide adenine dinucleotide phosphate hydrogen oxides; AIF: Apoptosis inducing factor; ROS: Reactive oxygen species; TGF: Transforming growth; IL: Interleukin; JAK: Janus kinase; STAT: Signal transducer and activator of transcription; MAPK: Mitogen-activated protein kinase.

Figure 3

The scheme of the potential roles of nicotinamide adenine dinucleotide phosphate hydrogen oxides in pancreatic cancer. ASK: Apoptosis signal regulating kinase; TGF: Transforming growth; SIRT: Silent information regulator; NF-κB: Nuclear factor kappa-B; ERK: Extracellular regulated protein kinases; SMAD: Drosophila mothers against decapentaplegic protein; NOX: Nicotinamide adenine dinucleotide phosphate hydrogen oxides; AIF: Apoptosis inducing factor; ROS: Reactive oxygen species; EMT: Epithelial to mesenchymal transition.