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Nitrolipids in kidney physiology and disease.

ABSTRACT: The kidneys are vital organs responsible for maintaining body fluid homeostasis within proper physiologic ranges. Kidney disease is an epidemic clinical problem causing significant morbidity and mortality, and current treatments are limited to renin-angiotensin system blockade or renal replacement therapy for the majority of affected individuals. There is a critical, unmet need for novel pharmacological agents to improve the outcome of patients with kidney disease. Nitro-oleic acid (NO2-OA) is an endogenously generated electrophilic compound with the capacity to modify thiols in proteins, altering their function. The most important targets appear to be the Keap1/Nrf2 and NF-?B pathways, which have widespread effects on antioxidant, detoxifying, and inflammatory responses in cells and tissues. Through these and potentially additional protective actions, NO2-OA may be capable of preserving or enhancing kidney function in acute and chronic kidney diseases.

SUBMITTER: Jobbagy S

PROVIDER: S-EPMC6163094 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Nitrolipids in kidney physiology and disease.

Jobbagy Soma S Tan Roderick J RJ

Nitric oxide : biology and chemistry 20180329

The kidneys are vital organs responsible for maintaining body fluid homeostasis within proper physiologic ranges. Kidney disease is an epidemic clinical problem causing significant morbidity and mortality, and current treatments are limited to renin-angiotensin system blockade or renal replacement therapy for the majority of affected individuals. There is a critical, unmet need for novel pharmacological agents to improve the outcome of patients with kidney disease. Nitro-oleic acid (NO<sub>2</su ...[more]

PMID: 29605557

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Project description:The biosynthetic secretory pathway is comprised of multiple steps, modifications and interactions that form a highly precise pathway of protein trafficking and secretion, that is essential for eukaryotic life. The general outline of this pathway is understood, however the specific mechanisms are still unclear. In the last 15 years there have been vast advancements in technology that enable us to advance our understanding of this complex and subtle pathway. Therefore, based on the strong foundation of work performed over the last 40 years, we can now build another level of understanding, using the new technologies available. The biosynthetic secretory pathway is a high precision process, that involves a number of tightly regulated steps: Protein folding and quality control, cargo selection for Endoplasmic Reticulum (ER) exit, Golgi trafficking, sorting and secretion. When deregulated it causes severe diseases that here we categorise into three main groups of aberrant secretion: decreased, excess and altered secretion. Each of these categories disrupts organ homeostasis differently, effecting extracellular matrix composition, changing signalling events, or damaging the secretory cells due to aberrant intracellular accumulation of secretory proteins. Diseases of aberrant secretion are very common, but despite this, there are few effective therapies. Here we describe ER exit sites (ERES) as key hubs for regulation of the secretory pathway, protein quality control and an integratory hub for signalling within the cell. This review also describes the challenges that will be faced in developing effective therapies, due to the specificity required of potential drug candidates and the crucial need to respect the fine equilibrium of the pathway. The development of novel tools is moving forward, and we can also use these tools to build our understanding of the acute regulation of ERES and protein trafficking. Here we review ERES regulation in context as a therapeutic strategy.

Dataset Information

Nitrolipids in kidney physiology and disease.

Publications

Nitrolipids in kidney physiology and disease.

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