scholarly journals Polyamine Catabolism in Acute Kidney Injury

2019 ◽  
Vol 20 (19) ◽  
pp. 4790 ◽  
Author(s):  
Kamyar Zahedi ◽  
Sharon Barone ◽  
Manoocher Soleimani
Keyword(s):  
Acute Kidney Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Therapeutic Interventions ◽  
Abrupt Decrease ◽  
Traumatic Injuries ◽  
Polyamine Catabolism ◽  
Intensive Care Patients ◽  
Mechanistic Basis

Acute kidney injury (AKI) refers to an abrupt decrease in kidney function. It affects approximately 7% of all hospitalized patients and almost 35% of intensive care patients. Mortality from acute kidney injury remains high, particularly in critically ill patients, where it can be more than 50%. The primary causes of AKI include ischemia/reperfusion (I/R), sepsis, or nephrotoxicity; however, AKI patients may present with a complicated etiology where many of the aforementioned conditions co-exist. Multiple bio-markers associated with renal damage, as well as metabolic and signal transduction pathways that are involved in the mediation of renal dysfunction have been identified as a result of the examination of models, patient samples, and clinical data of AKI of disparate etiologies. These discoveries have enhanced our ability to diagnose AKIs and to begin to elucidate the mechanisms involved in their pathogenesis. Studies in our laboratory revealed that the expression and activity of spermine/spermidine N1-acetyltransferase (SAT1), the rate-limiting enzyme in polyamine back conversion, were enhanced in kidneys of rats after I/R injury. Additional studies revealed that the expression of spermine oxidase (SMOX), another critical enzyme in polyamine catabolism, is also elevated in the kidney and other organs subjected to I/R, septic, toxic, and traumatic injuries. The maladaptive role of polyamine catabolism in the mediation of AKI and other injuries has been clearly demonstrated. This review will examine the biochemical and mechanistic basis of tissue damage brought about by enhanced polyamine degradation and discuss the potential of therapeutic interventions that target polyamine catabolic enzymes or their byproducts for the treatment of AKI.

scholarly journals Relevant Role of Von Willebrand Factor in Ischemia-Reperfusion Model of Acute Kidney Injury in Mice

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2243-2243
Author(s):  
Shiro Ono ◽  
Hideto Matsui ◽  
Masashi Noda ◽  
Shogo Kasuda ◽  
Yasunori Matsunari ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Blood Flow ◽  
Renal Blood Flow ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Relevant Role ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Acute kidney injury (AKI), an abrupt loss of renal function, is often seen in clinical settings and its mortality remains high even in the developed countries. An adhesive protein von Willebrand factor (VWF) plays a pivotal role in platelet thrombus formation and is recently understood as a key protein in a cross-talk between inflammation and thrombosis. Recent mouse model studies demonstrated that VWF-mediated thrombotic and inflammatory responses could play a role in the disease progression of myocardial infarction or brain stroke. Thus, we assumed that VWF may also be involved in the pathophysiology of AKI, the major cause of which could be an insufficient renal circulation and/or inflammatory cell infiltration in the kidney. To test this hypothesis, we studied the relevant role of VWF in AKI in mouse model of acute ischemia-reperfusion (I/R) kidney injury. All mice used were male, 8-12 weeks of age, healthy and whose right kidney was surgically removed by the standard mouse nephrectomy procedure 1 week prior to the kidney I/R experiment. The preliminary experiments confirmed that surgical removal of mouse right kidney did not affect their general conditions including renal functions. Mice were anesthetized with inhaled isoflurane and then placed in an abdominal position on a heating pad. Surgical incision was given on the left side of back and the left kidney was brought out and kept outside during the operation. Both renal artery and vein were clamped at the renal hilus by a clamping clip for 30 min ischemia. Then a clip was taken off to provoke the reperfusion of renal blood flow, which was monitored by Laser Doppler flowmetry (ALF21, Advance Co, Tokyo, Japan). The kidney was then put back in a body and skin incision was closed. The renal blood flow was measured again 30 h after reperfusion and mice were then sacrificed for blood collection. We compared 15 wild-type (WT) and 16 VWF-gene deleted (knock-out; KO) mice (from The Jackson Laboratory, Bar Harbor, ME). Excess blood loss was not observed in all mice (WT or KO) during whole surgical process. Although no difference was seen immediately after reperfusion, significantly (p < 0.05) higher renal blood flow at 30 h after reperfusion was confirmed in VWF-KO mice, as compared to WT (KO; 24.0±2.3 vs. WT; 15.1±1.46 ml/min/100g of kidney weight, and the reperfusion/base flow ratio: KO; 1.0±0.07 vs. WT; 0.6 ±0.07). Consistent with the renal blood flow data, the serum creatinine value at 30 h after reperfusion were significantly (p < 0.05) lower in VWF-KO mice than WT (KO; 2.77±0.11 vs. WT; 3.15±0.11 mg/dl). Our results suggest that VWF does play a role in the pathogenesis of AKI, in which VWF-dependent thrombotic or inflammatory responses may trigger thrombotic ischemia or endothelial damages of vascular bed in the kidney. Thus, proper functional regulation of VWF would be beneficial for better microcirculation and vessel functions in the kidney, suggesting a novel therapeutic potential against AKI. Disclosures No relevant conflicts of interest to declare.

scholarly journals Early lipid changes in acute kidney injury using SWATH lipidomics coupled with MALDI tissue imaging

2016 ◽  
Vol 310 (10) ◽  
pp. F1136-F1147 ◽  
Author(s):  
Sangeetha Rao ◽  
Kelly B. Walters ◽  
Landon Wilson ◽  
Bo Chen ◽  
Subhashini Bolisetty ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Acute Kidney Injury ◽  
Ischemia Reperfusion ◽  
Imaging Mass Spectrometry ◽  
Kidney Injury ◽  
Tissue Imaging ◽  
Maldi Ims ◽  
Hospital Morbidity ◽  
Rate Limiting

Acute kidney injury (AKI) is one of the leading causes of in-hospital morbidity and mortality, particularly in critically ill patients. Although our understanding of AKI at the molecular level remains limited due to its complex pathophysiology, recent advances in both quantitative and spatial mass spectrometric approaches offer new opportunities to assess the significance of renal metabolomic changes in AKI models. In this study, we evaluated lipid changes in early ischemia-reperfusion (IR)-related AKI in mice by using sequential window acquisition of all theoretical spectra (SWATH)-mass spectrometry (MS) lipidomics. We found a significant increase in two abundant ether-linked phospholipids following IR at 6 h postinjury, a plasmanyl choline, phosphatidylcholine (PC) O-38:1 (O-18:0, 20:1), and a plasmalogen, phosphatidylethanolamine (PE) O-42:3 (O-20:1, 22:2). Both of these lipids correlated with the severity of AKI as measured by plasma creatinine. In addition to many more renal lipid changes associated with more severe AKI, PC O-38:1 elevations were maintained at 24 h post-IR, while renal PE O-42:3 levels decreased, as were all ether PEs detected by SWATH-MS at this later time point. To further assess the significance of this early increase in PC O-38:1, we used matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) to determine that it occurred in proximal tubules, a region of the kidney that is most prone to IR injury and also rich in the rate-limiting enzymes involved in ether-linked phospholipid biosynthesis. Use of SWATH-MS lipidomics in conjunction with MALDI-IMS for lipid localization will help in elucidating the role of lipids in the pathobiology of AKI.

scholarly journals The role of podocyte damage in the etiology of ischemia-reperfusion acute kidney injury and post-injury fibrosis

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Yi Chen ◽  
Liyu Lin ◽  
Xuan Tao ◽  
Yankun Song ◽  
Jiong Cui ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Post Injury ◽  
Podocyte Damage

Role of GABAergic activity of sodium valproate against ischemia–reperfusion-induced acute kidney injury in rats

2013 ◽  
Vol 387 (2) ◽  
pp. 143-151 ◽  
Author(s):  
Ramanpreet Brar ◽  
Jaswinder Pal Singh ◽  
Tajpreet Kaur ◽  
Saroj Arora ◽  
Amrit Pal Singh
Keyword(s):  
Acute Kidney Injury ◽  
Sodium Valproate ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Gabaergic Activity

scholarly journals Gasdermin E deficiency attenuates acute kidney injury by inhibiting pyroptosis and inflammation

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Weiwei Xia ◽  
Yuanyuan Li ◽  
Mengying Wu ◽  
Qianqian Jin ◽  
Qian Wang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Caspase 3 ◽  
Inflammatory Diseases ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Tubular Epithelial Cells ◽  
Regulated Cell Death ◽  
Deficient Mice

AbstractPyroptosis, one kind of inflammatory regulated cell death, is involved in various inflammatory diseases, including acute kidney injury (AKI). Besides Gasdermin D (GSDMD), GSDME is a newly identified mediator of pyroptosis via the cleavage of caspase-3 generating pyroptotic GSDME-N. Here, we investigated the role of GSDME in renal cellular pyroptosis and AKI pathogenesis employing GSDME-deficient mice and human tubular epithelial cells (TECs) with the interventions of pharmacological and genetic approaches. After cisplatin treatment, GSDME-mediated pyroptosis was induced as shown by the characteristic pyroptotic morphology in TECs, upregulated GSDME-N expression and enhanced release of IL-1β and LDH, and decreased cell viability. Strikingly, silencing GSDME in mice attenuated acute kidney injury and inflammation. The pyroptotic role of GSDME was also verified in human TECs in vitro. Further investigation showed that inhibition of caspase-3 blocked GSDME-N cleavage and attenuated cisplatin-induced pyroptosis and kidney dysfunction. Moreover, deletion of GSDME also protected against kidney injury induced by ischemia-reperfusion. Taken together, the findings from current study demonstrated that caspase-3/GSDME-triggered pyroptosis and inflammation contributes to AKI, providing new insights into the understanding and treatment of this disease.

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