Renoprotective effect of azelnidipine in rats.
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To assess whether azelnidipine (AZN) exerts renoprotective effects, 20-week-old adult male stroke-prone spontaneously hypertensive rats (SHRsp) were treated with AZN 10 mg/kg/d (n=6), olmesartan (OLM) 3 mg/kg/d (n=4), hydralazine (HYD) 20 mg/kg/d (n=3), or water (control; n=5). Each test agent was administered by oral gavage for 12 weeks. Systolic blood pressure (SBP) was measured every 2 weeks and urinary protein excretion (UproV) every 3 weeks. At the age of 32 weeks, the rats were sacrificed and blood and kidneys collected for biochemical, histological, and immunohistochemical studies. All drug treatments significantly (p<0.05) reduced SBP, UproV, and blood biochemical parameters such as creatinine, total cholesterol, and blood urea nitrogen. Masson trichrome staining and immunohistochemical staining revealed significant (p<0.05) reductions of interstitial fibrosis, collagen type III, nicotinamide-adenine dinucleotide/nicotinamide-adenine dinucleotide phosphate oxidase, and p22(phox) and p47(phox) components expression in the AZN- and OLM-treated groups in comparison with rats treated with HYD and control animals. ED1, 4-hydroxy-2-nonenal (4-HNE), and heat shock protein (HSP)-47 expression was also reduced in the AZN- and OLM-treated groups versus in HYD and control animals. These results indicate that not only OLM but also AZN exerts renoprotective effects through inhibition of macrophage infiltration and antioxidant activity in SHRsp model of renal injury. (+info)
Autophagic elimination of misfolded procollagen aggregates in the endoplasmic reticulum as a means of cell protection.
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Autophagy eliminates a specific species of misfolded procollagen and plays a protective role in cell survival against ER stress.
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Type I collagen is one of the most abundant proteins in the human body and is essential for tissue formation. Mutations in collagen cause severe abnormalities in bone formation, including osteogenesis imperfecta. Although the mutant collagens are retained in the endoplasmic reticulum (ER) and are toxic to the cell, little is known about how they are removed from the ER. Using two independent cell lines that produce misfolded collagens, we recently demonstrated that procollagen, which is misfolded and accumulated as trimers, is eliminated through the autophagy-lysosomal pathway, not through the ER-associated degradation (ERAD) pathway. In contrast, misfolded procollagen monomer is degraded via ERAD. Moreover, autophagic elimination and ERAD occur independently and exert protective roles and promote cell survival. Thus, autophagy and ERAD, in concert, contribute to eliminating toxic species of misfolded and accumulated proteins from the ER. (+info)
Molecular targets for diabetes mellitus-associated erectile dysfunction.
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