Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Drug
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Target Concepts:
Gene/Protein
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Query: EC:4.2.1.22 (
cystathionine beta-synthase
)
965
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Elevated plasma homocysteine (Hcys) has been reported to participate in the development of arterial and
glomerular sclerosis
in Dahl salt-sensitive hypertensive (SS) rats. The mechanism resulting in hyperhomocysteinemia in these animals remains unknown. Disposal of Hcys in the kidneys plays an important role in regulating the plasma Hcys level. We, therefore, examined the activities and expressions of the enzymes involved in the metabolism of Hcys in the kidneys of SS rats, compared with that of Brown Norway rats and SSBN13 rats, a consomic subcolony of SS rats that carries a substituted chromosome 13 from Brown Norway rats. High-performance liquid chromatography analysis demonstrated that plasma Hcys levels were significantly higher in SS rats. The conversion of S-adenosylhomocysteine into Hcys via S-adenosylhomocysteine hydrolase by renal tissue was not different among these 3 rat strains. However, the metabolic rate of Hcys into cysteine was markedly reduced in the SS rat kidneys. The mRNA and protein levels of
cystathionine beta-synthase
(
CBS
), one of the key enzymes in the transsulfuration pathway in the kidneys, were significantly lower in SS rats. In microdissected nephron segments,
CBS
mRNA was shown to be mainly present in renal proximal tubules (PTs). The mRNA levels of
CBS
in the PTs were also significantly decreased in SS rats, accompanied by a reduced
CBS
activity in PTs. We conclude that hyperhomocysteinemia is associated with a decreased activity and expression of
CBS
in renal PTs because of the defect of chromosome 13 in SS rats.
...
PMID:Hyperhomocysteinemia associated with decreased renal transsulfuration activity in Dahl S rats. 1663 97
Despite substantial evidence indicating the association of hyperhomocysteinemia (hHcys) and end-stage renal disease (ESRD), the pathogenic role of increased plasma homocysteine (Hcys) levels in the progression of ESRD remains unclear. This review will briefly summarize recent findings regarding the role of hHcys in the development of
glomerulosclerosis
, the association of hHcys with reduced renal transsulfuration and Hcys-induced changes of redox signaling in the development of
glomerulosclerosis
in rat kidneys. Based on these results, it is concluded that hHcys is implicated in
glomerular sclerosis
in hypertension, elevated plasma Hcys in Dahl salt-sensitive (SS) hypertensive rats is due to downregulation of
cystathionine beta-synthase
(
CBS
) expression and consequent abnormality of transsulfuration in the kidney compared with normotensive rats. Hcys-induced superoxide (O(2)(*-)) production by activation of NADPH oxidase as a triggering mechanism contributes to the effects of Hcys on the homeostasis of extracellular matrix and consequent sclerosis in the glomeruli, and NADPH oxidase activation by Hcys is associated with enhanced Rac GTPase activity.
...
PMID:Hyperhomocysteinemia: association with renal transsulfuration and redox signaling in rats. 1806 50
