Mitochondria-Targeted Peptide Accelerates ATP Recovery and Reduces Ischemic Kidney Injury
Hazel H. Szeto,Shaoyi Liu,Yi Soong,Dunli Wu,Shaun Darrah,Feng Ying Cheng,Zhihong Zhao,Michael Ganger,Clara Y. Tow,Surya V. Seshan +9 more
TLDR
Treatment with SS-31 protected mitochondrial structure and respiration during early reperfusion, accelerated recovery of ATP, reduced apoptosis and necrosis of tubular cells, and abrogated tubular dysfunction, suggesting that it may protect against ischemic renal injury.Abstract:
The burst of reactive oxygen species (ROS) during reperfusion of ischemic tissues can trigger the opening of the mitochondrial permeability transition (MPT) pore, resulting in mitochondrial depolarization, decreased ATP synthesis, and increased ROS production. Rapid recovery of ATP upon reperfusion is essential for survival of tubular cells, and inhibition of oxidative damage can limit inflammation. SS-31 is a mitochondria-targeted tetrapeptide that can scavenge mitochondrial ROS and inhibit MPT, suggesting that it may protect against ischemic renal injury. Here, in a rat model of ischemia-reperfusion (IR) injury, treatment with SS-31 protected mitochondrial structure and respiration during early reperfusion, accelerated recovery of ATP, reduced apoptosis and necrosis of tubular cells, and abrogated tubular dysfunction. In addition, SS-31 reduced medullary vascular congestion, decreased IR-mediated oxidative stress and the inflammatory response, and accelerated the proliferation of surviving tubular cells as early as 1 day after reperfusion. In summary, these results support MPT as an upstream target for pharmacologic intervention in IR injury and support early protection of mitochondrial function as a therapeutic maneuver to prevent tubular apoptosis and necrosis, reduce oxidative stress, and reduce inflammation. SS-31 holds promise for the prevention and treatment of acute kidney injury.read more
Citations
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Mitochondria-targeted peptide SS-31 attenuates renal injury via an antioxidant effect in diabetic nephropathy
Yanjuan Hou,Shuangcheng Li,Ming Wu,Jinying Wei,Yunzhuo Ren,Chunyang Du,Haijiang Wu,Caili Han,Huijun Duan,Yonghong Shi +9 more
TL;DR: A protective effect of SS-31 against HG-induced renal injury via an antioxidant mechanism in diabetic nephropathy is demonstrated.
Journal ArticleDOI
Targeting Mitochondria and Reactive Oxygen Species-Driven Pathogenesis in Diabetic Nephropathy.
TL;DR: Current therapeutic interventions, mainly aimed at reducing or preventing mitochondrial-generated oxidative stress, improving mitochondrial antioxidant defense, and maintaining mitochondrial integrity, may deliver alternative approaches to halt or prevent diabetic kidney disease.
Journal ArticleDOI
Mitochondria-targeted therapies for acute kidney injury.
Luis Carlos Tábara,Jonay Poveda,Catalina Martin-Cleary,Rafael Selgas,Alberto Ortiz,Maria Dolores Sanchez-Niño +5 more
TL;DR: The morphological and functional mitochondrial changes during AKI are reviewed, as well as changes in the expression of mitochondrial genes and proteins, and the current status of novel therapeutic strategies specifically targeting mitochondria are summarized.
Journal ArticleDOI
Defective Mitochondrial Fatty Acid Oxidation and Lipotoxicity in Kidney Diseases.
TL;DR: The current state of knowledge on the role of mitochondrial FAO dysfunction in the pathophysiology of kidney diseases including AKI and CKD is explored and prospective views on developing therapeutic interventions based on mitochondrial energy metabolism are explored.
Journal ArticleDOI
Glutathione peroxidase 4 has a major role in protecting mitochondria from oxidative damage and maintaining oxidative phosphorylation complexes in gut epithelial cells.
TL;DR: It is concluded that in Caco-2 gut epithelial cells GPx4, through effects on AIF, plays a major role in maintaining the oxidative phosphorylation system and protecting mitochondria from oxidative damage.
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Journal ArticleDOI
Effect of Cyclosporine on Reperfusion Injury in Acute Myocardial Infarction
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