The Shear Stress/KLF2/Nrf2/ARE Pathway: A Hemodynamic Defense against Oxidative Stress

Many diseases have oxidative stress and inflammation as underlying pathological features, including metabolic and inflammatory/autoimmune disorders, diseases of the lung, liver, kidney, gastrointestinal tract, cardiovascular and nervous systems. A leading physiological mechanism for oxidative stress...

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Detalles Bibliográficos
Autores principales: Owen, John M., Dormer, Kenneth J.
Formato: Capítulo de libro
Lenguaje:inglés
Publicado: IntechOpen 2021
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Acceso en línea:https://www.intechopen.com/chapters/78504
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Sumario:Many diseases have oxidative stress and inflammation as underlying pathological features, including metabolic and inflammatory/autoimmune disorders, diseases of the lung, liver, kidney, gastrointestinal tract, cardiovascular and nervous systems. A leading physiological mechanism for oxidative stress is the nuclear erythroid-related factor 2-like 2/antioxidant response element (Nrf2/ARE) signaling pathway. It maintains intracellular homeostasis and protects cells from oxidative damage by inducing phase II detoxifying and oxidative-stress responsive genes. Nrf2 transcription factor functions as the key controller of the redox homeostatic gene regulatory network, and is tightly controlled by the repressor protein, Kelch-like ECH-associated protein 1 (Keap1). Pharmacological agents to inhibit Keap1 and boost effectiveness of the Nrf2/ARE pathway have been developed and more are in development. This chapter elucidates the importance of hemodynamic laminar shear stress in oxidative homeostasis and examines hemodynamic induction of the shear stress (SS)/Krupple-like factor2 (KLF2) /Nrf2/ARE pathway as a means to combat oxidative stress through hemodynamics.
ISBN:978-1-83969-716-6
DOI:10.5772/intechopen.99566