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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Journal ArticleDOI
Acute Kidney Injury.
TL;DR: This work reviews recent findings relating to the renal vasculature and cellular stress responses and identifies macrophages, growth-arrested tubular epithelial cells, the endothelium, and surrounding pericytes are key players in the progression to chronic disease.
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Expert consensus document: Mitochondrial function as a therapeutic target in heart failure
David Brown,Justin B. Perry,Mitchell E. Allen,Hani N. Sabbah,Hani N. Sabbah,Brian L. Stauffer,Saame Raza Shaikh,John G.F. Cleland,Wilson S. Colucci,Javed Butler,Adriaan A. Voors,Stefan D. Anker,Bertram Pitt,Bertram Pitt,Burkert Pieske,Gerasimos Filippatos,Stephen J. Greene,Mihai Gheorghiade +17 more
TL;DR: In this article, insights into the mechanisms of mitochondrial dysfunction in heart failure are presented, along with an overview of emerging treatments with the potential to improve the function of the failing heart by targeting mitochondria.
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Renal tubule injury: a driving force toward chronic kidney disease.
TL;DR: A better understanding of the mechanisms by which tubular injury drives inflammation and fibrosis is necessary for the development of therapeutics to halt the progression of chronic kidney disease.
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Renal ischemia/reperfusion injury; from pathophysiology to treatment.
Maryam Malek,Mehdi Nematbakhsh +1 more
TL;DR: This review summarizes some important potential mechanisms and therapeutic approaches in renal IRI and discusses the design of more targeted therapies to prevent and treatment the injury.
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First‐in‐class cardiolipin‐protective compound as a therapeutic agent to restore mitochondrial bioenergetics
TL;DR: SS‐31 represents a new class of compounds that can recharge the cellular powerhouse and restore bioenergetics and provides an update of its clinical development programme.
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