Involvement of hyperglycemia in deposition of aggregated protein in glomeruli of diabetic mice

Hirasawa, Yasushi; Matsui, Yoshio; Ohtsu, Shoko; Yamane, Katsu; Toyoshi, Tohru; Kyuki, Kohei; Sakai, Takayuki; Feng, Yibin; Nagamatsu, Tadashi

doi:10.1016/j.ejphar.2008.10.015

Cited by 4 publications

(2 citation statements)

References 33 publications

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“…Some reports showed that hyperglycemia contributes to an increase in the deposition of advanced glycation endproducts in glomeruli leading to mesangial expansion even early on in diabetes (9)(10)(11). that inflammation is particularly conducive to the progression of diabetic micro-and macro-angiopathy.…”

Section: Discussionmentioning

confidence: 99%

The up-regulated expression of both phospholipase A2 and cyclooxygenase-2 is involved in renal injury in streptozotocin-induced diabetic rats

Lu¹

2013

Acta Endo (Buc)

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Context. Recent evidence has stressed that many proinflammatory factors are particularly conducive to the progression of diabetic nephropathy, but the mechanisms underlying the changes are poorly understood.Objective. The purpose of this study was to investigate if up-regulated expression of both phospholipase A2 (PLA2) and cyclooxygenase-2 (COX-2) is involved in renal damage and micro-inflammatory state in streptozotocin-induced diabetic rats.Animals and methods. Sixteen Sprague Dawley rats were randomly divided into 2 groups: control group and diabetes group. Animals in diabetes group were treated with intraperitoneal injection of streptozotocin. Eight weeks later, rat renal tissue was studied with light and transmission electron microscopes, and PLA2 and COX-2 and their mRNA expression were examined by immunohistochemistry and reverse transcription polymerase chain reaction, respectively.Results. The renal pathological lesions in diabetes group were obvious, including increased amounts of mesangial matrix, thickening of the glomerular and tubular basement membranes and fusion and effacement of the adjacent podocyte foot processes. Infiltrating inflammatory cells were observed in the tubules. Compared with control group, the expression of cytosolic PLA2 and COX-2 was significantly increased in diabetes group.Conclusions. It uncovers that the PLA2-COX-2 pathway may lead to renal inflammation associated with renal damage in streptozotocin-induced diabetic rats.

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Section: Discussionmentioning

confidence: 99%

The up-regulated expression of both phospholipase A2 and cyclooxygenase-2 is involved in renal injury in streptozotocin-induced diabetic rats

Lu¹

2013

Acta Endo (Buc)

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“…Pioglitazone has been proposed to have anti-AGEs effect by inhibiting glycation, AGEs formation and protein cross-linking [177,178]. Studies employing pioglitazone as an anti-MG or anti-AGEs compound are not forthcoming and more evidence is needed to make definitive statements about the therapeutic potential of pioglitazone in this regard.…”

Section: Anti-mg and Anti-ages Compoundsmentioning

confidence: 99%

Aging: Drugs to Eliminate Methylglyoxal, a Reactive Glucose Metabolite, and Advanced Glycation Endproducts

Dhar¹,

Desai²

2012

Pharmacology

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Inhibition of tumor suppressor p53 preserves glycation-serum induced pancreatic beta-cell demise

Zhang

Huang

et al. 2016

Endocrine

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Tumor suppressor p53 is a transcriptional factor that determines cell fate in response to multiple stressors, such as oxidative stress and endoplasmic reticulum stress, in the majority of cells. However, its role in pancreatic beta cells is not well documented. Our previous research has revealed that glycation-serum (GS) induced pancreatic beta-cell demise through the AGEs-RAGE pathway. In the present study, we investigated the role of p53 in GS-related beta-cell demise. Using pancreatic islets beta-cell line INS-1 cells, we found that with GS treatment, the transcriptional activity of p53 was significantly evoked due to the increased amount of nuclear p53 protein. Resveratrol (RSV) was capable of further enhancing this transcriptional ability and consequently increased the population of dead beta cells under GS exposure. In contrast, inhibiting this transcriptional activity via p53 interference greatly protected beta cells from the damage provoked by GS, as well as damage strengthened by RSV. However, the pharmacological activation of PPARγ with troglitazone (TRO) only suppressed GS-induced, not RSV-induced, p53 activity. Moreover, the activation of PPARγ greatly preserved beta cells from GS-induced death. This protective effect recurred due to improved mitochondrial function with Bcl2 overexpression. Further, p53 activation could induce cellular apoptosis in primary rat islets. Our findings explore the broader role of p53 in regulating pancreatic beta-cell demise in the presence of GS and may provide a therapeutic target for the treatment and prevention of diabetes.

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Involvement of hyperglycemia in deposition of aggregated protein in glomeruli of diabetic mice

Cited by 4 publications

References 33 publications

The up-regulated expression of both phospholipase A2 and cyclooxygenase-2 is involved in renal injury in streptozotocin-induced diabetic rats

The up-regulated expression of both phospholipase A2 and cyclooxygenase-2 is involved in renal injury in streptozotocin-induced diabetic rats

Aging: Drugs to Eliminate Methylglyoxal, a Reactive Glucose Metabolite, and Advanced Glycation Endproducts

Inhibition of tumor suppressor p53 preserves glycation-serum induced pancreatic beta-cell demise

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