The Biochemical Basis of HGPRT Deficiency

Puig, Juan; Mateos, F

doi:10.1007/978-3-642-84962-6_3

Cited by 7 publications

(3 citation statements)

References 43 publications

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“…7 Affected individuals have hyperuricemia and a characteristic neurobehavioral phenotype comprising mental retardation, self-injurious behaviour and motor disability. [9][10][11] In addition, patients present a prominent loss of striatal dopamine. [9][10][11] In addition, patients present a prominent loss of striatal dopamine.…”

Section: Introductionmentioning

confidence: 99%

“…8 A common factor in Lesch-Nyhan is that patients exhibit a characteristically raised level of hypoxanthine in the urine, 9 plasma and cerebrospinal fluid. [9][10][11] In addition, patients present a prominent loss of striatal dopamine. 12 Bavaresco and colleagues 13,14 demonstrated that the in vitro administration of hypoxanthine induces oxidative stress in the striatum of rats and that intrastriatal injection alters striatal ectonucleotidase activities.…”

Section: Introductionmentioning

confidence: 99%

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Hypoxanthine induces oxidative stress in kidney of rats: protective effect of vitamins E plus C and allopurinol

Rodrigues

Roecker

Junges

et al. 2014

Cell Biochemistry & Function

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In the present study, we investigated the in vitro effect of hypoxanthine on the activities of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase, as well as on thiobarbituric-acid-reactive substances (TBA-RS), in the renal cortex and medulla of rats. Results showed that hypoxanthine, at a concentration of 10.0 μM, enhanced the activities of CAT and SOD in the renal cortex of 15-, 30- and 60-day-old rats, enhanced SOD activity in the renal medulla of 60-day-old rats and enhanced TBA-RS levels in the renal medulla of 30-day-old rats, as compared with controls. Furthermore, we also verified the influence of allopurinol (an inhibitor of xanthine oxidase), as well as of the antioxidants, trolox and ascorbic acid on the effects elicited by hypoxanthine on the parameters tested. Allopurinol and/or administration of antioxidants prevented most alterations caused by hypoxanthine in the oxidative stress parameters evaluated. Data suggest that hypoxanthine alters antioxidant defences and induces lipid peroxidation in the kidney of rats; however, in the presence of allopurinol and antioxidants, some of these alterations in oxidative stress were prevented. Our findings lend support to a potential therapeutic strategy for this condition, which may include the use of appropriate antioxidants for ameliorating the damage caused by hypoxanthine.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hypoxanthine induces oxidative stress in kidney of rats: protective effect of vitamins E plus C and allopurinol

Rodrigues

Roecker

Junges

et al. 2014

Cell Biochemistry & Function

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“…In addition, patients present a prominent loss of striatal dopamine (Jinnah and Friedmann, 2001). A common factor in Lesch–Nyhan is that patients exhibit a characteristically raised level of hypoxanthine in urine (Harkness et al, 1988), plasma and cerebrospinal fluid (Rosenbloom et al, 1967; Harkness et al, 1988; Puig and Mateos, 1993). Although the underlying mechanisms of brain dysfunction in Lesch–Nyhan are poorly understood, the accumulation of oxypurines such as hypoxanthine has been proposed to contribute to the neurological dysfunction present in this disease (Dasheiff, 1980; Kisch et al, 1985; Visser et al, 2000; Ma et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Intrastriatal hypoxanthine administration affects Na⁺,K⁺‐ATPase, acetylcholinesterase and catalase activities in striatum, hippocampus and cerebral cortex of rats

Bavaresco

Chiarani

Wajner

et al. 2006

Intl J of Devlp Neuroscience

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The aim of this study was to investigate the effects of a single intrastriatal injection of hypoxanthine, the major metabolite accumulating in Lesch-Nyhan disease, on Na(+),K(+)-ATPase, acetylcholinesterase and catalase activities in striatum, cerebral cortex and hippocampus of rats at different post-infusion periods. Adult Wistar rats were divided in two groups: (1) vehicle-injected group (control) and (2) hypoxanthine-injected group. For Na(+),K(+)-ATPase activity determination, the animals were sacrificed 3h, 24h and 7 days after drug infusion. For the evaluation of acetylcholinesterase and catalase activities, the animals were sacrificed 30min, 3h, 24h and 7 days after hypoxanthine infusion. Results show regional and time dependent effects of hypoxanthine on Na(+),K(+)-ATPase, acetylcholinesterase and catalase activities. The in vitro effect of hypoxanthine on the same enzymes in striatum was also investigated. Results showed that hypoxanthine inhibited Na(+),K(+)-ATPase, but not the activities of acetylcholinesterase and catalase in rat striatum. We suggest that these modification on cerebral biochemical parameters (Na(+),K(+)-ATPase, acetylcholinesterase and catalase activities) induced by intrastriatal administration of hypoxanthine in all cerebral structures studied, striatum, hippocampus and cerebral cortex, could be involved in the pathophysiology of Lesch-Nyhan disease.

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Hypoxanthine impairs morphogenesis and enhances proliferation of a neuroblastoma model of Lesch Nyhan syndrome

Margaret

Stacey

Connolly

2001

J of Neuroscience Research

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Extracellular purines have essential roles in neuronal development; hence, disruptions in their metabolism as reported in Lesch Nyhan syndrome (LNS) could result in developmental abnormalities. The deficiency of hypoxanthine-guanine phosphoribosyl transferase (HGPRT) in LNS leads to increased hypoxanthine and uric acid production. We have reported that HGPRT-deficient B103-4C neuroblastoma, a neuronal model of LNS, proliferated less and differentiated more than their HGPRT-positive B103 counterparts. Here, we sought to determine whether differences in proliferation and differentiation would occur when these cells were cultured in the presence of hypoxanthine or in a hypoxanthine-/serum-free chemically defined media (NBMN2). In media with 1% serum, hypoxanthine (50 microM) significantly increased the proliferation of both cell lines with a greater effect on B103-4C cells. In 1% serum media, hypoxanthine increased differentiation of B103 but decreased B103-4C differentiation. In NBMN2, B103 proliferated far more than B103-4C, but both cell types differentiated to the same extent. These results are interpreted to suggest that elevated levels of central nervous system (CNS) hypoxanthine as reported in LNS may affect neuronal development, and to implicate hypoxanthine and abnormal neuronal development as causative factors in the etiology of LNS.

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The Biochemical Basis of HGPRT Deficiency

Cited by 7 publications

References 43 publications

Hypoxanthine induces oxidative stress in kidney of rats: protective effect of vitamins E plus C and allopurinol

Hypoxanthine induces oxidative stress in kidney of rats: protective effect of vitamins E plus C and allopurinol

Intrastriatal hypoxanthine administration affects Na⁺,K⁺‐ATPase, acetylcholinesterase and catalase activities in striatum, hippocampus and cerebral cortex of rats

Hypoxanthine impairs morphogenesis and enhances proliferation of a neuroblastoma model of Lesch Nyhan syndrome

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The Biochemical Basis of HGPRT Deficiency

Cited by 7 publications

References 43 publications

Hypoxanthine induces oxidative stress in kidney of rats: protective effect of vitamins E plus C and allopurinol

Hypoxanthine induces oxidative stress in kidney of rats: protective effect of vitamins E plus C and allopurinol

Intrastriatal hypoxanthine administration affects Na+,K+‐ATPase, acetylcholinesterase and catalase activities in striatum, hippocampus and cerebral cortex of rats

Hypoxanthine impairs morphogenesis and enhances proliferation of a neuroblastoma model of Lesch Nyhan syndrome

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Intrastriatal hypoxanthine administration affects Na⁺,K⁺‐ATPase, acetylcholinesterase and catalase activities in striatum, hippocampus and cerebral cortex of rats