Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Most potent mutators heretofore detected in Escherichia coli are associated with defects in epsilon subunit of DNA polymerase III, encoded by the dnaQ gene. To elucidate the role of the alpha subunit, the catalytic subunit of the polymerase, in maintaining the high fidelity of DNA replication, we isolated a mutator mutant, the mutation (dnaE173) of which resides on the dnaE gene, encoding the alpha subunit. The dnaE173 mutant was unable to grow in salt-free L broth at temperatures exceeding 44.5 degrees C and exhibited an increased frequency of spontaneous mutations, 1,000 to 10,000-fold the wild type level, at permissive temperatures. The mutator effect of dnaE173 mutation is dominant over the wild type allele. These phenotypes are caused by a single base substitution, resulting in one amino acid change, Glu612 (GAA)----Lys(AAA), in the alpha subunit molecule. DNA polymerase III purified from the dnaE173 mutant contained both alpha and epsilon subunits, in a normal molar ratio. We found no differences between wild type and mutant polymerases in the Vmax, thermolabilities, and salt sensitivities. However, the apparent Km for the substrate nucleotide of the mutant polymerase was 1/6 of that determined with the wild type polymerase. Although the mutant polymerase retained a normal level of 3'----5' exonuclease activity, the proofreading capacity determined by "turnover assay" was significantly lower in the mutant polymerase, as compared with findings in the normal enzyme. It seems likely that the enhanced mutability in the dnaE173 strain results from, at least in part, a defect in the editing function of DNA polymerase III, and further suggests that a portion of the alpha subunit in which the amino acid change resides may be important for the proper setting of the two subunits at the replication fork so as to facilitate efficient editing during the DNA replication.
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PMID:A strong mutator effect caused by an amino acid change in the alpha subunit of DNA polymerase III of Escherichia coli. 200 48

Recent advances in the operative management of aortic aneurysms have resulted in a decreased rate of morbidity and mortality. In 1972, we hypothesized that a further reduction in operative mortality might be obtained with controlled perioperative fluid management based on data provided by the thermistor-tipped pulmonary artery balloon catheter. From 1972 to 1979 a flow directed pulmonary artery catheter was inserted in each of 110 consecutive patients prior to elective or urgent repair of nonruptured infrarenal aortic aneurysms. The slope of the left ventricular performance curve was determined preoperatively by incremental infusions of salt-poor albumin and Ringer's lactate solution. With each increase in the pulmonary arterial wedge pressure (PAWP), the cardiac index (CI) was measured. The PAWP was then maintained intra- and postoperatively at levels providing optimal left ventricular performance for the individual patient. There were no 30-day operative deaths among the patients in this series and only one in-hospital mortality (0.9%), four months following surgery. The five-year cumulative survival rate for patients in the present series was 84%, a rate which does not differ significantly from that expected for a normal age-corrected population. Since the patient population was unselected and there were no substantial alterations in operative technique during the present period, these improved results support the hypothesis that operative mortality attending the elective or urgent repair of abdominal aortic aneurysm can be minimized by maintenance of optimal cardiac performance with careful attention to fluid therapy during the perioperative period.
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PMID:Aortic aneurysm repair. Reduced operative mortality associated with maintenance of optimal cardiac performance. 741 34

We report a new compound heterozygous frameshift mutation in the type II 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) gene in a Pakistanian female child with the salt-wasting form of 3 beta-HSD deficiency congenital adrenal hyperplasia. The child, born with clitoral enlargement, manifesting salt-wasting adrenal crisis, and public hair growth during infancy, was treated with hormonal replacement therapy. The etiology of her congenital adrenal hyperplasia, however, was not defined. Two of her siblings, as well as one paternal cousin with ambiguous genitalia and palpable gonads and another paternal cousin with normal female genitalia, had symptoms of adrenal crisis and died during early infancy. Thus, although the family history suggested possible 3 beta-HSD deficiency disorder, suppressed adrenal function caused by excess glucocorticoid therapy in this child at 7 yr of age did not allow hormonal diagnosis. To confirm 3 beta-HSD deficiency, we sequenced the type II 3 beta-HSD gene in the patient, her family, and the parents of her decreased paternal cousins. The type II 3 beta-HSD gene region of a putative promoter, exons I, II, III, and IV, and exon-intron boundaries were amplified by PCR and sequenced in all subjects. The DNA sequence of the child revealed a single nucleotide deletion at codon 318 [ACA (Thr)-->AA] in exon IV in one allele, and two nucleotide deletions at codon 273 [AAA(Lys)-->A] in exon IV in the other allele. The remaining gene sequences were normal. The codon 318 mutation was found in one allele from the father, brother, and parents of the deceased paternal cousins. The codon 273 mutation was found in one allele of the mother and a sister. These findings confirmed inherited 3 beta-HSD deficiency in the child caused by the compound heterozygous type II 3 beta-HSD gene mutation. Both codon 273 and 318 mutations yielding frameshift and premature stop codons at codons 279 and 367, respectively, are predicted to result in an altered and truncated type II 3 beta-HSD protein, thereby causing salt-wasting 3 beta-HSD deficiency in the patient. The type II 3 beta-HSD gene findings and clinical history of her family members suggest that the patient's deceased siblings were likely affected males with the same compound heterozygous mutations of the gene as in the proband, whereas the deceased cousins were likely affected with the homozygous codon 318 mutation in the gene.
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PMID:A new compound heterozygous frameshift mutation in the type II 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) gene causes salt-wasting 3 beta-HSD deficiency congenital adrenal hyperplasia. 855 Jul 66

We studied the effect of excessive salt intake on vascular lesion development in hypertensive transgenic mice that overproduce angiotensin II, ie, Tsukuba hypertensive mice (THM). At 6 weeks of age, THM and C57BL/6J (controls) were given either 1% sodium chloride ("salt-loaded") drinking water or tap water for 30 days. Salt-loaded THM, but not controls, suffered frequent thoracic or abdominal cavity hemorrhage. THM mortality after 7 days of salt loading was 23%; after 30 days of salt loading, it rose to 67%. Hemorrhaging occurred due to the development of aortic aneurysm and rupture at the aortic arch and aorta near the renal arteries. Vascular lesions progressed with structural degeneration of the aortic media. Electronmicroscopic analysis revealed that intact THM already exhibited vascular remodeling consisting of vascular smooth muscle cells (VSMCs) with developed organelles and an increased extracellular matrix. Salt-loaded THM suffered aggravated vascular hypertrophy and vascular structure destruction by plasma material invasion, necrosis of VSMCs possessing extremely swollen cytoplasm and abundant organelles, and interlamellar bleeding, resulting in aortic aneurysm and eventual rupture. Interestingly, blood pressure levels and heart rates in salt-loaded THM did not differ significantly from those of controls; plasma renin activity between drinking regimens was also comparable between the two groups. Drinking volume and the concentration of atrial natriuretic peptide (ANP) in plasma, however, were significantly higher in salt-loaded THM than in intact THM. In addition to aneurysm localization, the findings regarding drinking volume and plasma ANP suggest that aortic aneurysm and rupture in salt-loaded THM occurred as the result of an unknown mechanical stress, other than blood pressure, on the aortic wall. High salt ingestion is involved in the development of thoracic and abdominal aortic aneurysm in the presence of hypertension in the activated renin-angiotensin system. THM should therefore serve as a useful animal model for studying the pathogenesis of aortic aneurysm accompanied by hypertension.
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PMID:Salt-sensitive aortic aneurysm and rupture in hypertensive transgenic mice that overproduce angiotensin II. 975 50

Degradation of the elastic media is a hallmark of abdominal aortic aneurysms (AAAs). We examined the expression of 2 elastolytic matrix metalloproteinases (MMPs), MMP-2 and MMP-9, in AAA aortic tissues compared with those from atherosclerotic occlusive disease (AOD) and nondiseased control tissues. Quantitative competitive reverse transcription-polymerase chain reaction and gelatin zymography showed increased MMP-9 mRNA and protein in both AAA and AOD tissues compared with those in control tissue, but there was no significant difference between AAA and AOD. In contrast, MMP-2 mRNA and protein levels were significantly higher in AAA than in AOD or control tissues. Sequential extraction of the MMPs from the aortic tissue with a physiological salt solution, 2% dimethylsulfoxide (DMSO), and 10 mol/L urea showed that large amounts of MMP-2 and MMP-9 were bound to the matrix. The most conspicuous finding was that the levels of MMP-2 were significantly elevated in the DMSO fraction in AAA tissues compared with AOD and control tissues. In addition, a large portion of MMP-2 found in the DMSO and urea fractions was in the active 62-kDa form, indicating that the precursor of MMP-2 in AAA is largely activated locally and binds to the tissue matrix tightly. By immunolocalization, MMP-9 was found to be primarily produced by macrophages and MMP-2 by mesenchymal cells. The production of MMP-2 was prominent when mesenchymal cells were surrounded by inflammatory cells, suggesting paracrine modulation of MMP-2 expression in AAAs. These observations emphasize that MMP-2 participates in the progression of AAAs by degrading aortic tissue matrix components.
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PMID:Matrix metalloproteinase-2 production and its binding to the matrix are increased in abdominal aortic aneurysms. 976 36

Archaea are a valuable source of enzymes for industrial and scientific applications because of their ability to survive extreme conditions including high salt and temperature. Thanks to advances in molecular biology and genetics, archaea are also attractive hosts for metabolic engineering. Understanding how energy-dependent proteases and chaperones function to maintain protein quality control is key to high-level synthesis of recombinant products. In archaea, proteasomes are central players in energy-dependent proteolysis and form elaborate nanocompartments that degrade proteins into oligopeptides by processive hydrolysis. The catalytic core responsible for this proteolytic activity is the 20S proteasome, a barrel-shaped particle with a central channel and axial gates on each end that limit substrate access to a central proteolytic chamber. AAA proteins (ATPases associated with various cellular activities) are likely to play several roles in mediating energy-dependent proteolysis by the proteasome. These include ATP binding/hydrolysis, substrate binding/unfolding, opening of the axial gates, and translocation of substrate into the proteolytic chamber.
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PMID:Archaeal proteasomes: potential in metabolic engineering. 1294 49

The roles of two adjacent genes in the Staphylococcus aureus chromosome with functions in starvation survival and the response to stressful conditions have been characterized. One of these, hprT, encoding a hypoxanthine-guanine phosphoribosyltransferase homologue, was initially identified in a transposon mutagenesis screen. Mutation of hprT affects starvation survival in amino-acid-limiting conditions and the ability of S. aureus to grow in high-salt concentrations. Downstream of hprT is ftsH, which encodes a membrane-bound, ATP- and Zn(2+)-dependent 'AAA'-type protease. Mutation of ftsH in S. aureus leads to pleiotropic defects including slower growth, sensitivity to salt, acid, methyl viologen and potassium tellurite stresses, and reduced survival in amino-acid- or phosphate-limiting conditions. Both hprT-lacZ and ftsH-lacZ gene fusions are expressed maximally in the post-exponential phase of growth. Although secretion of exoproteins is not affected, an ftsH mutant is attenuated in a murine skin lesion model of pathogenicity.
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PMID:Role of the hprT-ftsH locus in Staphylococcus aureus. 1476 15

A full-length salt-induced transcript homologous to SKD1 (suppressor of K(+) transport growth defect) of the AAA (ATPase associated with a variety of cellular activities)-type ATPase family has been identified from the halophyte Mesembryanthemum crystallinum (ice plant). The expression of mcSKD1 was induced by 200 mM NaCl or higher in cultured ice plant cells. When cultured ice plant cells were grown in a high K(+) (42.6 mM) medium, the level of mcSKD1 expression decreased. At the whole plant level, constitutive expression of mcSKD1 was observed in roots, stems, leaves and floral organs. Addition of 400 mM NaCl increased the transcript level in roots and stems. The expression of atSKD1 , a homologue gene in Arabidopsis , was down regulated by salt stress. Under salt stress, mcSKD1 was preferentially expressed in the outer cortex of roots and stems and in the epidermal bladder cells of leaves. The mcSKD1 transcript was constitutively expressed in placenta and integuments of the developing floral buds. Expression of the full-length or C-terminal deletion of mcSKD1 was able to complement the K(+) uptake-defect phenotype in mutant Saccharomyces cerevisiae , which is defective in high- and low-affinity K(+) uptake. Deletion of the N-terminal coiled-coil motif of mcSKD1, a structure required for membrane association, resulted in greatly reduced K(+) transport. Expression of mcSKD1 also increased the salt-tolerant ability of yeast mutants and either N- or C-terminal deletion decreased the efficiency. The physiological relevancies of mcSKD1 for K(+) uptake under high salinity environments are discussed.
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PMID:Tissue-specific expression and functional complementation of a yeast potassium-uptake mutant by a salt-induced ice plant gene mcSKD1. 1560 58

Misfolded secretory proteins are transported across the endoplasmic reticulum (ER) membrane into the cytosol for degradation by proteasomes. A large fraction of proteasomes in a cell is associated with the ER membrane. We show here that binding of proteasomes to ER membranes is salt sensitive, ATP dependent, and mediated by the 19S regulatory particle. The base of the 19S particle, which contains six AAA-ATPases, binds to microsomal membranes with high affinity, whereas the 19S lid complex binds weakly. We demonstrate that ribosomes and proteasomes compete for binding to the ER membrane and have similar affinities for their receptor. Ribosomes bind to the protein conducting channel formed by the Sec61 complex in the ER membrane. We co-precipitated subunits of the Sec61 complex with ER-associated proteasome 19S particles, and found that proteoliposomes containing only the Sec61 complex retained proteasome binding activity. Collectively, our data suggest that the Sec61 channel is a principal proteasome receptor in the ER membrane.
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PMID:The protein translocation channel binds proteasomes to the endoplasmic reticulum membrane. 1597 33

The full-length 2213-bp ftsH (filamentation temperature-sensitive H) cDNA was cloned from the cDNA library of heat-shocked tomato leaves. According to an open reading frame of 2019-bp, the deduced protein precursor was predicted to target chloroplast. The putative AAA (ATPases associated with diverse cellular activities) domain and the Zn(2+)-binding domain, characteristic of FtsH metalloproteases family, were found in the FtsH-like protein. Most similar to the FtsH6 of Arabidopsis thaliana, the tomato ftsH-like gene was named as Lycopersicon esculentum filamentation temperature-sensitive H6 (LeftsH6). Purified FtsH degraded casein but not BSA in vitro, whereas a FtsH mutant with the Glu(472) in the zinc-binding motif replaced by Gln had lost the protease activity. A single copy of LeftsH6 was detected in tomato genome by Southern blot analysis. Northern and Western blot analyses revealed consistently the heat-inducible character of the LeftsH6 gene. No LeftsH6 expression was detected after cold, salt, drought or light stress. The results provided the first experimental evidence of the existence of heat-inducible ftsH gene in higher plants.
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PMID:Cloning and molecular characteristic of the metalloprotease gene LeftsH6 from tomato. 1647 33


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