Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study we report the generation of superoxide anion and hydrogen peroxide by a water-insoluble protein fraction from aged human lenses in response to UVA light. Irradiation with 1.5 kJ cm-2 of UVA light ( > 338 nm) over a 1 hr period caused the formation of 20 +/- 0.1 microM superoxide radical and 37 +/- 0.5 microM hydrogen peroxide. A linear photolysis of SH-groups (21 nmol ml-1, 26%). His (117 nmol ml-1, 26%) and Trp (72 nmol ml-1, 27%) residues was seen following 60 min of irradiation. The addition of SOD, however, had no effect on the photolytic destruction of any of these amino acid residues. Incubation of the human WISS proteins and bovine alpha-crystallin in the presence of 43-49 microM of O2- generated in a xanthine oxidase/hypoxanthine system over a 1 hr period, caused no loss of histidine, little or no loss of tryptophan and loss of 7-9 nmol ml-1 of sulfhydryl groups with both proteins. This argues that O2- can only account for the destruction of at most 4-8 nmol SH-groups in human water-insoluble proteins following 1 hr of UVA irradiation.
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PMID:The generation of superoxide anion by the UVA irradiation of human lens proteins. 898 65

An R120G mutation in alphaB-crystallin (CryAB(R120G)) causes desmin-related myopathy (DRM). In mice with cardiomyocyte-specific expression of the mutation, CryAB(R120G)-mediated DRM is characterized by CryAB and desmin accumulations within cardiac muscle, mitochondrial deficiencies, activation of apoptosis, and heart failure (HF). Excessive production of reactive oxygen species (ROS) is often a hallmark of HF and treatment with antioxidants can sometimes prevent the progression of HF in terms of contractile dysfunction and cardiomyocyte survival. It is unknown whether blockade of ROS is beneficial for protein misfolding diseases such as DRM. We addressed this question by blocking the activity of xanthine oxidase (XO), a superoxide-generating enzyme that is upregulated in our model of DRM. The XO inhibitor oxypurinol was administered to CryAB(R120G) mice for a period of 1 or 3 months. Mitochondrial function was dramatically improved in treated animals in terms of complex I activity and conservation of mitochondrial membrane potential. Oxypurinol also largely restored normal mitochondrial morphology. Surprisingly, however, cardiac contractile function and cardiac compliance were unimproved, indicating that the contractile deficit might be independent of mitochondrial dysfunction and the initiation of apoptosis. Using magnetic bead microrheology at the single cardiomyocyte level, we demonstrated that sarcomeric disarray and accumulation of the physical aggregates resulted in significant changes in the cytoskeletal mechanical properties in the CryAB(R120G) cardiomyocytes. Our findings indicate that oxypurinol treatment largely prevented mitochondrial deficiency in DRM but that contractility was not improved because of mechanical deficits in passive cytoskeletal stiffness.
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PMID:Biochemical and mechanical dysfunction in a mouse model of desmin-related myopathy. 1929 43