Abstract
The mitochondria are a major source of reactive oxygen species (ROS). Superoxide anion (O2•–) is produced by the process of oxidative phosphorylation associated with glucose, amino acid, and fatty acid metabolism, resulting in the production of adenosine triphosphate (ATP) in the mitochondria. Excess production of reactive oxidants in the mitochondria, including O2•–, and its by-product, peroxynitrite (ONOO–), which is generated by a reaction between O2•– with nitric oxide (NO•), alters cellular function via oxidative modification of proteins, lipids, and nucleic acids. Mitochondria maintain an antioxidant enzyme system that eliminates excess ROS; manganese superoxide dismutase (Mn-SOD) is one of the major components of this system, as it catalyzes the first step involved in scavenging ROS. Reduced expression and/or the activity of Mn-SOD results in diminished mitochondrial antioxidant capacity; this can impair the overall health of the cell by altering mitochondrial function and may lead to the development and progression of kidney disease. Targeted therapeutic agents may protect mitochondrial proteins, including Mn-SOD against oxidative stress-induced dysfunction, and this may consequently lead to the protection of renal function. Here, we describe the biological function and regulation of Mn-SOD and review the significance of mitochondrial oxidative stress concerning the pathogenesis of kidney diseases, including chronic kidney disease (CKD) and acute kidney injury (AKI), with a focus on Mn-SOD dysfunction.
Highlights
The prevalence of chronic kidney disease (CKD) has been increasing worldwide (Eckardt et al, 2013)
Mitochondrial oxidative stress contributes to the pathogenesis of kidney disease, including acute kidney injury (AKI), CKD, and the AKI to CKD transition, and mitochondriatargeted drugs may suppress the onset or progression of kidney disease (Figure 3)
manganese superoxide dismutase (Mn-superoxide dismutase (SOD)) dysfunction results in a net increase in reactive oxygen species (ROS) and generates a vicious cycle in which mitochondrial oxidative stress is amplified, as Mn-SOD becomes a target of dysfunctional oxidative modification
Summary
The prevalence of chronic kidney disease (CKD) has been increasing worldwide (Eckardt et al, 2013). Mn-SOD and Kidney Disease better understanding of the underlying fundamental mechanisms related to progression and onset of both CKD and AKI. Previous reports have shown that mitochondrial oxidative stress may be directly linked to mechanisms underlying the onset and progression of both CKD and AKI (Che et al, 2014; He et al, 2017). Among ROS scavenging enzymes in the mitochondrial matrix, Mn-SOD has a primary responsibility for O2− scavenging within mitochondria; as such, dysfunction of Mn-SOD results in mitochondrial oxidative stress. We consider the significance of mitochondrial oxidative stress on the pathogenesis of kidney disease, including CKD and AKI, with a focus on the role of Mn-SOD dysfunction. Sp1 and AP-2 regulate the basal level of sod gene transcription via antagonistic mechanisms at the proximal promoter region
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