Role of Glyoxalase System on Methylglyoxal Induced Peritoneal Thickeness in Glyoxalase Transgenic Rats

The formation and accumulation of advanced glycation endproducts (AGEs) are related to diabetes and other age-related diseases. Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is the major precursor in the formation of AGEs. MGO is mainly formed as a byproduct of glycolysis. Under physiological circumstances, MGO is detoxified by the glyoxalase system into D-lactate, with glyoxalase I (GLO1) as the key enzyme in the anti-glycation defence. New insights indicate that increased levels of MGO and the major MGO-derived AGE, methylglyoxal-derived hydroimidazolone 1 (MG-H1), and dysfunctioning of the glyoxalase system are linked to several age-related health problems, such as diabetes, cardiovascular disease, cancer and disorders of the central nervous system. The present review summarizes the mechanisms through which MGO is formed, its detoxification by the glyoxalase system and its effect on biochemical pathways in relation to the development of age-related diseases. Although several scavengers of MGO have been developed over the years, therapies to treat MGO-associated complications are not yet available for application in clinical practice. Small bioactive inducers of GLO1 can potentially form the basis for new treatment strategies for age-related disorders in which MGO plays a pivotal role.

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Expression of an angiotensin-(1–7)-producing fusion protein produces cardioprotective effects in rats

Physiological Genomics ◽

10.1152/physiolgenomics.00227.2003 ◽

2004 ◽

Vol 17 (3) ◽

pp. 292-299 ◽

Cited By ~ 135

Author(s):

Robson A. S. Santos ◽

Anderson J. Ferreira ◽

Ana Paula Nadu ◽

Aline N. G. Braga ◽

Alvair Pinto de Almeida ◽

...

Keyword(s):

Fusion Protein ◽

Cardiac Contractility ◽

Renin Angiotensin System ◽

Transgenic Rats ◽

Specific Expression ◽

Angiotensin System ◽

Angiotensin Converting Enzyme 2 ◽

Cardioprotective Effects ◽

Hemodynamic Measurements

Angiotensin-(1–7) [ANG-(1–7)] is a recently described heptapeptide product of the renin-angiotensin system. Because biosynthesis of ANG-(1–7) increases in animals treated with cardioprotective drugs and inactivation of the gene for angiotensin converting enzyme 2 [an enzyme involved in the biosynthesis of ANG-(1–7)] leads to the development of cardiac dysfunction, it has been suggested that ANG-(1–7) has cardioprotective properties. To directly test this possibility, we have generated transgenic rats that chronically overproduce ANG-(1–7) by using a novel fusion protein methodology. TGR(A1–7)3292 rats show testicular-specific expression of a cytomegalovirus promoter-driven transgene, resulting in a doubling of circulating ANG-(1–7) compared with nontransgenic control rats. Radiotelemetry hemodynamic measurements showed that transgenic rats presented a small but significant increase in daily and nocturnal heart rate and a slight but significant increase in daily and nocturnal cardiac contractility estimated by dP/d t measurements. Strikingly, TGR(A1–7)3292 rats were significantly more resistant than control animals to induction of cardiac hypertrophy by isoproterenol. In addition, transgenic rats showed a reduced duration of reperfusion arrhythmias and an improved postischemic function in isolated Langendorff heart preparations. These results support a cardioprotective role for circulating ANG-(1–7) and provide a novel tool for evaluating the functional role of ANG-(1–7).

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Abstract MP04: Cardiac ACE2/Angiotensin-(1-7) in Rats Expressing Human Angiotensinogen Gene

Hypertension ◽

10.1161/hyp.66.suppl_1.mp04 ◽

2015 ◽

Vol 66 (suppl_1) ◽

Author(s):

Jasmina Varagic ◽

Jessica VonCannon ◽

Sarfaraz Ahmad ◽

Michael Bader ◽

Carlos M Ferrario

Keyword(s):

Cardiac Hypertrophy ◽

Cardiac Tissue ◽

Male Rats ◽

Ang Ii ◽

Sprague Dawley ◽

Transgenic Rats ◽

Sd Rats ◽

Agt Gene ◽

Tissue Angiotensin

When compared to Sprague Dawley (SD) control rats, transgenic rats expressing the human angiotensinogen (AGT) gene [TGR(hAGT)L1623] exhibit hypertension associated with cardiac hypertrophy and higher cardiac tissue angiotensin (Ang) II. Whether the hypertension and cardiac hypertrophy in these rats expressing the human AGT are related to a non-canonical pathway for Ang II formation or suppression of the counter regulatory mechanism mediated by ACE2 and Ang-(1-7) has not been established. Consequently, cardiac peptides were determined by RIA in 9 [TGR(hAGT)L1623] and 11 SD male rats (17 weeks of age). ACE2 activities in homogenized heart tissues were determined by HPLC. Cardiac Ang II content was four times higher (37.05 ± 5.04 vs. 9.62 ± 0.93 fmol/mg protein; p <0.0001) while the Ang-(1-7) level increased only 1.3 times (18.02 ± 1.62 vs 13.37 ± 1.74 fmol/mg protein; p=0.06) in TGR(hAGT)L1623 rats when compared with SD rats. Although, the Ang II/Ang-(1-7) ratio was higher in transgenic rats harboring the human AGT gene (2.10 ± 0.27 vs 0.90 ± 0.19; p <0.005), ACE2 activities between these two strains of animals were not different (12.21 ± 0.76 vs. 10.80 ± 0.91 fmol/min/mg; p >0.05). Since human AGT protein is not cleaved by rat renin, our data continues to support the view that hypertension and cardiac hypertrophy in this transgenic strain are induced by activation of a non-renin mechanism rather than a primary suppression of the compensatory Ang II degrading pathway mediated by ACE2. Further studies are necessary to determine the role of enzymes affecting Ang-(1-7) metabolism in the observed inadequate balance between Ang II and Ang-(1-7).

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The Role of Glyoxalase System in Renal Hypoxia

Advances in Experimental Medicine and Biology - Oxygen Transport to Tissue XXXI ◽

10.1007/978-1-4419-1241-1_6 ◽

2009 ◽

pp. 49-55 ◽

Cited By ~ 13

Author(s):

Reiko Inagi ◽

Takanori Kumagai ◽

Toshiro Fujita ◽

Masaomi Nangaku

Keyword(s):

Glyoxalase System

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Role of the Glyoxalase System in Alzheimer’s Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-180413 ◽

2018 ◽

Vol 66 (3) ◽

pp. 887-899 ◽

Cited By ~ 3

Author(s):

Lianying Jiang ◽

Jiafeng Wang ◽

Zhigang Wang ◽

Wenhui Huang ◽

Yixia Yang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Glyoxalase System

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Role of γ-Adducin in Actin Cytoskeleton Rearrangements in Podocyte Pathophysiology

AJP Renal Physiology ◽

10.1152/ajprenal.00423.2020 ◽

2020 ◽

Author(s):

Wenjun Gao ◽

Yedan Liu ◽

Letao Fan ◽

Baoying Zheng ◽

Joshua R. Jefferson ◽

...

Keyword(s):

Actin Cytoskeleton ◽

Vascular Function ◽

Renal Cortex ◽

Transgenic Rats ◽

Focal Adhesion Proteins ◽

Foot Process ◽

And Function ◽

Cytoskeleton Rearrangements ◽

Renal Vascular

We recently reported that the enhanced susceptibility to chronic kidney disease (CKD) in the FHH rat is caused, at least in part, by a mutation in γ-adducin (ADD3) that attenuates renal vascular function. The present study explored whether Add3 contributes to the modulation of podocyte structure and function using FHH and FHH.Add3 transgenic rats. The expression of ADD3 on the membrane of primary podocytes isolated from FHH was reduced compared with FHH.Add3 transgenic rats. We found that F-actin nets, which are typically localized in the lamellipodia, replaced unbranched stress fibers in conditionally immortalized mouse podocytes transfected with Add3 DsiRNA and primary podocytes isolated from FHH rats. There were increased F/G-actin ratio and expression of the Arp2/3 complexes throughout FHH podocytes in association with reduced synaptopodin and RhoA but enhanced Rac1 and CDC42 expression in the renal cortex, glomeruli and podocytes of FHH rats. The expression of Nephrin at the slit diaphragm and the levels of focal adhesion proteins ITGA3 and ITGB1 were decreased in the glomeruli of FHH rats. Cell migration was enhanced and adhesion was reduced in podocytes of FHH rats, as well as in immortalized mouse podocyte transfected with Add3 DsiRNA. Mean arterial pressures were similar in FHH and FHH.Add3 transgenic rats at 16-week of age; however, FHH rats exhibited enhanced proteinuria associated with podocyte foot process effacement. These results demonstrate that reduced ADD3 function in FHH rats alters baseline podocyte pathophysiology by rearrangement of the actin cytoskeleton at the onset of proteinuria in young animals.

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