Hypercholesterolemia is a prerequisite for puromycin inducible damage in mouse kidney

Cheng, Zhu-Zhu; Pätäri, Anu; Aalto‐Setälä, Katriina; Novikov, Dmitry S.; Schlöndorff, Detlef; Holthöfer, Harry

doi:10.1046/j.1523-1755.2003.00726.x

Cited by 21 publications

(20 citation statements)

References 40 publications

(8 reference statements)

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“…As previously described [12,13], injection of 150 mg/kg PAN could not induce either proteinuria or any other serum abnormalities of nephrotic syndrome in these mice (data not shown). On the other hand, a higher dosage of PAN (450 mg/kg) did induce proteinuria in all of the tested mouse strains, as shown in figure 2.…”

Section: Resultssupporting

confidence: 79%

A Novel Nuclear Factor κB Inhibitor, Dehydroxymethylepoxyquinomicin, Ameliorates Puromycin Aminonucleoside-Induced Nephrosis in Mice

et al. 2013

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Background/Aims: Minimal-change nephrotic syndrome (MCNS) is a kidney disease defined by selective proteinuria and hypoalbuminemia occurring in the absence of cellular glomerular infiltrates or immunoglobulin deposits. Recent observations suggest that nuclear factor κB (NF-κB) of podocyte is strongly associated with the development of proteinuria in MCNS. Dehydroxymethylepoxyquinomicin (DHMEQ) is a novel NF-κB inhibitor that potently inhibits DNA-binding activity of NF-κB, resulting in several therapeutic effects in various pathological conditions. We conducted this study to ask whether DHMEQ may ameliorate the nephrosis in mice induced by puromycin aminonucleoside (PAN), which is considered to be an animal model for MCNS. Methods/Results: Pretreatment with DHMEQ alleviated the proteinuria and reversed the serum abnormalities in mice nephrosis induced by 450 mg/kg of PAN. Increased serum interleukin-6 level in PAN-induced nephrosis was also completely suppressed by DHMEQ. Electron microscopic analyses of glo-meruli indicated that DHMEQ can inhibit the podocyte foot process effacement via blocking the translocation of podocyte NF-κB from cytoplasm to nucleus. Conclusions: These results suggest that DHMEQ can be a potential therapeutic agent for MCNS.

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Section: Resultssupporting

confidence: 79%

A Novel Nuclear Factor κB Inhibitor, Dehydroxymethylepoxyquinomicin, Ameliorates Puromycin Aminonucleoside-Induced Nephrosis in Mice

et al. 2013

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“…We used male mice because female mice are relatively resistant. Previous studies successfully induced PAN nephrosis in mice after a high dosage (500 mg/kg subcutaneously), 34 after a high-cholesterol diet, 35 or with multiple doses (20 mg/kg subcutaneously or 90 mg/kg intraperitoneally). 36,37 We found that PAN led to an increase in UAE associated with foot process effacement and a reduction in podocin and ZO-1 mRNA expression.…”

Section: Discussionmentioning

confidence: 99%

Activation of Adenosine 2A Receptors Preserves Structure and Function of Podocytes

Awad

Rouse

Liu

et al. 2008

Journal of the American Society of Nephrology

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Adenosine 2A receptor (A 2A R) activation was recently shown to be renoprotective in diabetic nephropathy. A 2A R are found in glomeruli and have been shown to associate with the podocyte cytoskeletal protein ␣-actinin-4, but the effect of their activation on podocyte structure and function is unknown. Podocyte injury was induced in C57BL/6 mice with puromycin aminonucleoside, and the selective A 2A R agonist ATL313 was found to attenuate the resulting albuminuria and foot process fusion. The selective A 2A R antagonist ZM241385 reversed the effects of ATL313. In vitro, A 2A R mRNA and protein were expressed in a conditionally immortalized podocyte cell line, and A 2A R-like immunoreactivity co-localized with the actin cytoskeleton. Treatment with ATL313 also blocked the increased podocyte permeability to albumin and disruption of the actin cytoskeleton that accompanied puromycin aminonucleosideinduced injury in vitro. ATL313 was ineffective, however, in the presence of the A 2A R antagonist and in A 2A R-deficient podocytes. It was concluded that A 2A R activation reduces glomerular proteinuria, at least in part, by preserving the normal structure of podocyte foot processes, slit diaphragms, and actin cytoskeleton.

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“…Typically, PA studies utilize male Sprague-Dawley rats weighing between 90 and 200 g. Despite slight differences in quantity and onset, proteinuria and ultrastructural changes are reproducible among many different rat strains. Although there are a few exceptions, historically mice have been resistant to PAN (29,41,120).…”

Section: Rat Model Of Puromycin Aminonucleoside Nephrosismentioning

confidence: 99%

Inducible rodent models of acquired podocyte diseases

Pippin

Brinkkoetter²,

Cormack-Aboud³

et al. 2009

American Journal of Physiology-Renal Physiology

233

263

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Pippin JW, Brinkkoetter PT, Cormack-Aboud FC, Durvasula RV, Hauser PV, Kowalewska J, Krofft RD, Logar CM, Marshall CB, Ohse T, Shankland SJ. Inducible rodent models of acquired podocyte diseases. Am J Physiol Renal Physiol 296: F213-F229, 2009. First published September 10, 2008 doi:10.1152/ajprenal.90421.2008.-Glomerular diseases remain the leading cause of chronic and end-stage kidney disease. Significant advances in our understanding of human glomerular diseases have been enabled by the development and better characterization of animal models. Diseases of the glomerular epithelial cells (podocytes) account for the majority of proteinuric diseases. Rodents have been extensively used experimentally to better define mechanisms of disease induction and progression, as well as to identify potential targets and therapies. The development of podocyte-specific genetically modified mice has energized the research field to better understand which animal models are appropriate to study acquired podocyte diseases. In this review we discuss inducible experimental models of acquired nondiabetic podocyte diseases in rodents, namely, passive Heymann nephritis, puromycin aminonucleoside nephrosis, adriamycin nephrosis, liopolysaccharide, crescentic glomerulonephritis, and protein overload nephropathy models. Details are given on the model backgrounds, how to induce each model, the interpretations of the data, and the benefits and shortcomings of each. Genetic rodent models of podocyte injury are excluded.glomerulus; animal models HISTOLOGICAL ANALYSIS is a cornerstone for studying mechanisms of glomerular disease. However, analysis in human disease is limited by a relative paucity of tissue availability. Renal biopsies are only pursued if a presumptive diagnosis cannot be established on clinical grounds. Tissue sampling is typically restricted to the time of disease presentation and is rarely performed in follow-up, providing a mere snapshot of disease course.Animal models have significantly advanced our understanding of the pathogenesis of glomerular disease by overcoming these hurdles. Serial assessment of renal tissue in experimental models affords the opportunity to study development and progression of disease over time. Furthermore, the host response to injury may be deliberately modified, for example, through pharmacological intervention, selective disruption (knockout strategies), or overexpression (transgenic strategies) of a particular gene, allowing for mechanistic evaluations. A variety of animal species have been employed in the study of glomerular disease, but rodent models are preferred due to lower cost, maintenance requirements, and short gestational periods. Although both rats and mice are utilized, there are some important advantages and disadvantages for each (Table 1). The development of transgenic technology has proven an invaluable tool in elucidating the function of individual genes in health and disease. However, they cannot replace experimental models in furthering our understanding of the mechanisms...

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Hypercholesterolemia is a prerequisite for puromycin inducible damage in mouse kidney

Abstract: Hypercholesterolemia, possibly via LPO, is a prerequisite for puromycin-inducible glomerular damage in the mouse. Furthermore, nephrin protein and mRNA levels appear to be candidate markers of glomerular damage in the mouse.

Cited by 21 publications

References 40 publications

A Novel Nuclear Factor κB Inhibitor, Dehydroxymethylepoxyquinomicin, Ameliorates Puromycin Aminonucleoside-Induced Nephrosis in Mice

A Novel Nuclear Factor κB Inhibitor, Dehydroxymethylepoxyquinomicin, Ameliorates Puromycin Aminonucleoside-Induced Nephrosis in Mice

Activation of Adenosine 2A Receptors Preserves Structure and Function of Podocytes

Inducible rodent models of acquired podocyte diseases

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Hypercholesterolemia is a prerequisite for puromycin inducible damage in mouse kidney

Abstract: Hypercholesterolemia, possibly via LPO, is a prerequisite for puromycin-inducible glomerular damage in the mouse. Furthermore, nephrin protein and mRNA levels appear to be candidate markers of glomerular damage in the mouse.

Cited by 21 publications

References 40 publications

A Novel Nuclear Factor &#954;B Inhibitor, Dehydroxymethylepoxyquinomicin, Ameliorates Puromycin Aminonucleoside-Induced Nephrosis in Mice

A Novel Nuclear Factor &#954;B Inhibitor, Dehydroxymethylepoxyquinomicin, Ameliorates Puromycin Aminonucleoside-Induced Nephrosis in Mice

Activation of Adenosine 2A Receptors Preserves Structure and Function of Podocytes

Inducible rodent models of acquired podocyte diseases

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Product

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A Novel Nuclear Factor κB Inhibitor, Dehydroxymethylepoxyquinomicin, Ameliorates Puromycin Aminonucleoside-Induced Nephrosis in Mice

A Novel Nuclear Factor κB Inhibitor, Dehydroxymethylepoxyquinomicin, Ameliorates Puromycin Aminonucleoside-Induced Nephrosis in Mice