PubMed · 14141239
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
L E VOYER, R S MERECH. 1964. [WATER-ELECTROLYTE CHANGES].. https://pubmed.ncbi.nlm.nih.gov/14141239/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Insoluble Abeta1-42 is the main component of the amyloid plaque. We have previously demonstrated that exposure to low pH can confer the molten globule state on soluble Abeta1-42 in vitro [Biochem. J. 361 (2000) 547] and unfolding experiments with guadinine hydrochloride (GdnHCl) have now confirmed this observation. The molten globule state of the protein has many biological properties and understanding the mechanisms of its formation is an important step in devising a therapeutic strategy for Alzheimer's disease (AD). We therefore investigated the ability of a series of synthetic eight-residue peptides derived from Abeta1-42 to inhibit the acid-induced aggregation of Abeta1-42 and identified the potent peptides to be Abeta15-22, Abeta16-23 and Abeta17-24. A1-antichymotrypsin, a member of the serine proteinase inhibitor (serpin) family is another major component of the amyloid plaque. In the present study, we investigated the proteolytic activity of Abeta1-42 against casein at different pHs. Chemical modification of amino acid residues in Abeta1-42 indicated that serine and histidine residues, but not aspartic acid, are necessary for enzymatic activity, suggesting that it is a serine proteinase. Amino acid substitution studies indicate that glutamic acids at positions 11 and 22 participate indirectly in proteolysis and we surmise that amino acid residues 29-42 are required to stabilize the conformer. A study of metal ions suggested that Cu2+ affected the enzymatic activity, but Zn2+ and Fe2+ did not. Interestingly, Abeta14-21 and Abeta15-22 were the only peptides that inhibited the proteolytic activity of Abeta42. Therefore, Abeta15-22 may control both aggregation of Abeta1-42 at acidic pH and its proteolytic activity at neutral pH. Consequently, we suggest that it may be of use in the therapy of Alzheimer's disease.
OBJECTIVE: To estimate renal function and lipid metabolism in pregnant renal transplant recipients. STUDY DESIGN: The study covered 64 women during the third trimester of pregnancy including 33 renal transplant recipients (the study group) and 31 healthy women (the control group). Serum concentrations of uric acid, urea, creatinine, electrolytes, total protein, albumin, acid-base balance and blood cell count were examined to assess renal function. Moreover, the levels of the following lipid metabolism parameters were estimated: (1) total lipids (TL), (2) total LDL fraction (TLDL), (3) total cholesterol (TCh), (4) free cholesterol (fCh), (5) free/total cholesterol (fCh/TCh) ratio, (6) phospholipids (PhL), (7) total cholesterol/phospholipids (fCh/PhL) ratio, (8) triglycerides (TG), (9) HDL-cholesterol (HDL-Ch), (10) LDL-cholesterol (LDL-Ch) and (11) LDL-Ch/HDL-Ch ratio. 'The effect of immunosuppressants (cyclosporine, prednisone and azathioprine) on serum lipid levels was estimated in the study group. The mean maternal age, gestational age and BMI did not differ in both groups. RESULTS: Pregnant renal transplant recipients presented mild renal insufficiency during the third trimester resulting in the increase in serum level of uric acid (P<0.001), urea (P<0.001), creatinine (P<0.001), and Cl- (P<0.001). Proteinuria (1.19+/-1.9 g/24 h) leading to hypoproteinemia (P<0.001) and hypoalbuminemia (P<0.05) confirmed renal function impairment in the study group. Additionally, the diagnosis of renal insufficiency was supported by mild acidosis reflected by a drop in pH (P<0.001). standard HCO3- (P<0.001) and base excess (P<0.001). The women with renal grafts presented vital lipid metabolism disturbances illustrated by the elevated levels of: (1) TL by 72% (P<0.001), (2) TLDL by 21% (P<0.001), (3) TCh by 16% (P<0.001), (4) fCh by 34% (P<0.001), (5) fCh/TCh ratio by 21% (P<0.001), (6) PhL by 28% (P<0.001), (7) TG by 53% (P<0.001), (8) LDL-Ch by 13% (P<0.05) and (9) LDL-Ch/HDL-Ch ratio by 23% (P<0.001). No difference in HDL-Ch level between the two groups was found. Hyperlipidemia in pregnant kidney recipients was associated with immunosuppressive treatment and depended on cyclosporine treatment regimen. Treatment with azathioprine and prednisone was associated with elevated serum levels of examined lipids. CONCLUSION: Serum lipid abnormalities are significantly influenced by the administered dosages of immunosuppressants.
Hypoxia and acidosis occur in a wide variety of physiological and pathological settings that include muscle stress, tumour development and ischaemic disorders. A central element in the adaptive response to cellular hypoxia is HIF (hypoxia-inducible factor), a transcription factor that activates an array of genes implicated in oxygen homeostasis, tumour vascularization and ischaemic preconditioning. HIF is activated by hypoxia, but undergoes degradation by the VHL (von Hippel-Lindau) tumour suppressor protein in the presence of oxygen. Here, we demonstrate that hypoxia induction or normoxic acidosis can neutralize the function of VHL by triggering its nucleolar sequestration, a regulatory mechanism of protein function that is observed rarely. VHL is confined to nucleoli until neutral pH conditions are reinstated. Nucleolar sequestration of VHL enables HIF to evade destruction in the presence of oxygen and activate its target genes. Our findings suggest that an increase in hydrogen ions elicits a transient and reversible loss of VHL function by promoting its nucleolar sequestration.