MRI of renal oxygenation and function after normothermic ischemia-reperfusion injury

2010 ◽  
Vol 24 (2) ◽  
pp. 194-200 ◽  
Author(s):  
Marlies Oostendorp ◽  
Eva E. de Vries ◽  
Jos M. G. M. Slenter ◽  
Carine J. Peutz-Kootstra ◽  
Maarten G. Snoeijs ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
And Function

scholarly journals Beclin 1/Bcl-2 complex-dependent autophagy activity modulates renal susceptibility to ischemia-reperfusion injury and mediates renoprotection by Klotho

2020 ◽  
Vol 318 (3) ◽  
pp. F772-F792 ◽  
Author(s):  
Peng Li ◽  
Mingjun Shi ◽  
Jenny Maique ◽  
Joy Shaffer ◽  
Shirley Yan ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Genetic Manipulation ◽  
Protein Complexes ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Beclin 1 ◽  
Klotho Protein ◽  
And Function ◽  
Autophagy Activity

Klotho- and beclin 1-driven autophagy extends life. We examined the role of beclin 1 in modifying acute kidney injury (AKI) and whether beclin 1 mediates Klotho’s known renoprotective action in AKI. AKI was induced by ischemia-reperfusion injury in mice with different levels of autophagy activity by genetic manipulation: wild-type (WT) mice with normal beclin 1 expression and function, mice with normal beclin 1 levels but high activity through knockin of gain-of-function mutant beclin 1 ( Becn1F121A), mice with low beclin 1 levels and activity caused by heterozygous global deletion of beclin 1 ( Becn1+/−), or mice with extremely low beclin 1 activity from knockin of the mutant constitutively active beclin 1 inhibitor Bcl-2 ( Bcl2AAA). Klotho was increased by transgenic overexpression ( Tg-Kl) or recombinant Klotho protein administration. After ischemia-reperfusion injury, Becn1F121A mice (high autophagy) had milder AKI and Becn1+/− and Bcl2AAA mice (low autophagy) had more severe AKI than WT mice. Tg-Kl mice had milder AKI, but its renoprotection was partially attenuated in Becn1+/− ;Tg-Kl mice and was significantly reduced, although not completely abolished, in Bcl2AAA;Tg-Kl mice. Recombinant Klotho protein conferred more renoprotection from AKI in WT mice than in Becn1+/− or Bcl2AAA mice. Klotho reduced beclin 1/Bcl-2 protein complexes and increased autophagy activity, but this effect was less prominent in mice or cells with Bcl2AAA. Transfected Bcl2AAA or Becn1F123A decreased or increased autophagy activity and rendered cells more susceptible or more resistant to oxidative cytotoxicity, respectively. In conclusion, beclin 1 confers renoprotection by activating autophagy. Klotho protects the kidney partially via disruption of beclin 1/Bcl-2 interactions and enhancement of autophagy activity.

scholarly journals Beyond Preconditioning: Postconditioning as an Alternative Technique in the Prevention of Liver Ischemia-Reperfusion Injury

2016 ◽  
Vol 2016 ◽  
pp. 1-21 ◽  
Author(s):  
Kassiani Theodoraki ◽  
Iosifina Karmaniolou ◽  
Aliki Tympa ◽  
Marios-Konstantinos Tasoulis ◽  
Constantinos Nastos ◽  
...  
Keyword(s):  
Blood Flow ◽  
Reperfusion Injury ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Liver Ischemia ◽  
Neutrophil Accumulation ◽  
Postoperative Function ◽  
Early Reperfusion ◽  
And Function

Liver ischemia/reperfusion injury may significantly compromise hepatic postoperative function. Various hepatoprotective methods have been improvised, aiming at attenuating IR injury. With ischemic preconditioning (IPC), the liver is conditioned with a brief ischemic period followed by reperfusion, prior to sustained ischemia. Ischemic postconditioning (IPostC), consisting of intermittent sequential interruptions of blood flow in the early phase of reperfusion, seems to be a more feasible alternative than IPC, since the onset of reperfusion is more predictable. Regarding the potential mechanisms involved, it has been postulated that the slow intermittent oxygenation through controlled reperfusion decreases the burst production of oxygen free radicals, increases antioxidant activity, suppresses neutrophil accumulation, and modulates the apoptotic cascade. Additionally, favorable effects on mitochondrial ultrastructure and function, and upregulation of the cytoprotective properties of nitric oxide, leading to preservation of sinusoidal structure and maintenance of blood flow through the hepatic circulation could also underlie the protection afforded by postconditioning. Clinical studies are required to show whether biochemical and histological improvements afforded by the reperfusion/reocclusion cycles of postconditioning during early reperfusion can be translated to a substantial clinical benefit in liver resection and transplantation settings or to highlight more aspects of its molecular mechanisms.

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