Histamine H receptor antagonism prevents the progression of diabetic nephropathy in male DBA2/J mice.

Due to the incidence of diabetes and the related morbidity of diabetic nephropathy, identification of new therapeutic strategies represents a priority. In the last few decades new and growing evidence on the possible role of histamine in diabetes has been provided. In particular, the histamine receptor HR is emerging as a new promising pharmacological target for diabetic nephropathy.

Histamine type 1-receptor activation by low dose of histamine undermines human glomerular slit diaphragm integrity.

Histamine has been reported to decrease the ultrafiltration coefficient, which inversely correlates with glomerular permselectivity, however the mechanism(s) underling this effect have never been investigated. This study aimed to assess whether histamine could exert a direct detrimental effect on podocyte permeability and the possible involvement of two key proteins for the glomerular slit diaphragm (SD) integrity, zonula occludens-1 (ZO-1) and P-cadherin. The effect of histamine (100 pM-1000nM) on coloured podocytes junctional integrity was evaluated functionally by a transwell assay of monolayer permeability and morphologically by electron microscopy.

A computational analysis of S-(2-succino)cysteine sites in proteins.

The adduction of fumaric acid to the sulfhydryl group of certain cysteine (Cys) residues in proteins via a Michael-like reaction leads to the formation of S-(2-succino)cysteine (2SC) sites. Although its role remains to be fully understood, this post-translational Cys modification (protein succination) has been implicated in the pathogenesis of diabetes/obesity and fumarate hydratase-related diseases. In this study, theoretical approaches to address sequence- and 3D-structure-based features possibly underlying the specificity of protein succination have been applied to perform the first analysis of the available data on the succinate proteome.

Fumaric acid esters prevent the NLRP3 inflammasome-mediated and ATP-triggered pyroptosis of differentiated THP-1 cells.

Fumaric acid esters (FAEs) exert therapeutic effects in patients with psoriasis and multiple sclerosis, however their mode of action remains elusive. Pyroptosis is a caspase-1-dependent pro-inflammatory form of programmed cell death, mediated by the activation of inflammasomes. To understand the pharmacological basis of the therapeutic effects of FAEs, the anti-pyroptotic activity of dimethyl fumarate (DMF) and its hydrolysis metabolite monomethyl fumarate (MMF) was studied in a model of NLRP3 inflammasome-mediated pyroptosis of human macrophages.

H3 receptor renal expression in normal and diabetic rats.

Introduction: To extend our previous observation of H4R upregulation in the kidney of diabetic rats, we evaluated in the same specimens the presence of the H3R.

Materials And Methods: Kidney specimens from 24 8-week-old male Wistar rats (12 non-diabetic and 12 diabetic animals) were processed for both immunohistochemical and immunofluorescence analyses.

Results And Conclusion: H3R is expressed in the apical membrane by collecting duct cells in the kidney of rats and it is significantly increased in diabetic animals.

Histamine receptor expression in human renal tubules: a comparative pharmacological evaluation.

Objective And Design: The aim of this study is to evaluate the expression of the histamine receptors, particularly focusing on the H4R in human renal tubules.

Material: The ex vivo evaluation was carried on specimens from human renal cortex. Primary and immortalized tubular epithelial cells (TECs) and the HK-2 cell line were used as in vitro models.