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Biomedical subjects

J Moskovitz

Publications and source records attributed to J Moskovitz.

23 records · Page 2Linked to original sources

Escherichia coli peptide methionine sulfoxide reductase gene: regulation of expression and role in protecting against oxidative damage.

The Escherichia coli peptide methionine sulfoxide reductase gene (msrA) encodes a single-subunit polypeptide of 212 amino acid residues (M. A. Rahman, H. Nelson, H. Weissbach, and N. Brot, J. Biol. Chem. 267:15549-15551, 1992). RNA blot analysis showed that the gene is transcribed into an mRNA of about 850 nucleotides. The promoter region was characterized, and the transcription initiation site was identified by primer extension. The synthesis of the MsrA protein increased about threefold in a growth-phase-dependent fashion. In an attempt to define the in vivo role of msrA, a chromosomal disruption was constructed. This mutant was more sensitive to oxidative stress, suggesting that oxidation of methionine in proteins plays an important role in oxidative damage.

Base Sequence↗

Characterization of the 30-kDa enzyme from red blood cells that cleaves ubiquitin-protein conjugates.

A 30-kDa enzyme from red blood cells responsible for the recycling of free Ubiquitin has been characterized. This enzyme was previously known to have a Ubiquitin-C-terminal hydrolase activity on adducts of Ubiquitin to small compounds. In this study it was shown that the 30-kDa enzyme contained Ubiquitin-C-terminal hydrolase activity toward biosynthetic precursors of Ub as well as isopeptidase activity toward Ubiquitin histone conjugates. Detailed inhibition experiments with Ubiquitin aldehyde, iodoacetamide, and heat inactivation showed that the enzyme isopeptidase activity was affected differently from its hydrolase activity.

Aldehydes↗

An evaluation of autonomic nervous system function in patients with Prader-Willi syndrome.

OBJECTIVE: Prader-Willi syndrome (PWS) is a complex multisystem genetic disorder in which many cardinal features may have a neurologically based pathophysiology involving both the central and peripheral components of the autonomic nervous system. Autonomic nervous system function was studied noninvasively in a group of subjects with PWS and control subjects to determine whether autonomic nervous system dysfunction exists as part of the PWS. DESIGN/SETTING: This cross-sectional study was performed in the neurophysiology laboratory at a tertiary care facility. METHODS: Evaluation included anthropometric measurements and calculation of a body mass index (BMI). Simultaneous electrocardiography and serial recordings of pulse rate and systolic/diastolic mean arterial blood pressures during orthostatic maneuvers were taken. Pupillary response to the instillation of dilute pilocarpine and measurements of plasma norepinephrine at rest and after standing were also obtained. Results were analyzed using two-tailed t tests, Fisher exact test, analysis of variance, and analysis of covariance adjusting for age, gender, and BMI. PATIENTS: There were 14 subjects with PWS (8 female, 6 male; aged 4 to 40 years, mean age 16 years) and 8 control subjects (4 female, 4 male; aged 5 to 37 years, mean age 19 years). RESULTS: Abnormal findings were obtained only in subjects with PWS. Analysis of covariance adjusting for age, gender, and BMI revealed a trend for subjects with PWS to have lower resting diastolic blood pressure (P < .09) and significantly less change in diastolic blood pressure after standing (P < .02). Subjects with PWS had significantly greater BMI than did control subjects (P < .001), which correlated significantly with all pulse rate measurements where the greater the BMI the higher the pulse rate at rest (r = .25, P < .04) and the lower the pulse rate after arising from lying to standing at both 15 and 30 seconds (r = .17, P < .1; r = .55, P < .08 respectively). Pupillary constriction of 2 mm or more was seen in 7 of 14 subjects with PWS and in no control subjects (P < .004). The 30:15 R-R interval ratio was abnormal in 6 of 14 subjects with PWS and in no control subjects (P < .03). CONCLUSIONS: These results suggest that patients with PWS have a detectable underlying autonomic dysfunction characterized principally by diminished parasympathetic nervous system activity.

Adolescent↗

Oxidation of methionine in proteins: roles in antioxidant defense and cellular regulation.

The roles of methionine residues in proteins have not been well defined, but a review of available studies leads to the conclusion that methionine, like cysteine, functions as an antioxidant and as a key component of a system for regulation of cellular metabolism. Methionine is readily oxidized to methionine sulfoxide by many reactive species. The oxidation of surface exposed methionines thus serves to protect other functionally essential residues from oxidative damage. Methionine sulfoxide reductases have the potential to reduce the residue back to methionine, increasing the scavenging efficiency of the system. Reversible covalent modification of amino acids in proteins provides the mechanistic basis for most systems of cellular regulation. Interconversion of methionine and methionine sulfoxide can function to regulate the biological activity of proteins, through alteration in catalytic efficiency and through modulation of the surface hydrophobicity of the protein.

Animals↗