title: Inhibition of creatine kinase activity by cystine in the kidney of young rats.
abstract: Nephropathic cystinosis is a lethal genetic disease caused by a lysosomal transport disorder leading to intralysosomal cystine accumulation in all tissues. Cystinosis is the most common inherited cause of Fanconi syndrome, but the mechanisms by which cystine causes tissue damage are not fully understood. Thiol-containing enzymes are critical for renal energy metabolism and may be altered by disulfides like cystine. Therefore, in the present study our main objective was to investigate the in vivo and in vitro effects of cystine on creatine kinase, which contains critical thiol groups in its structure, in the kidney of young Wistar rats. We observed that cystine inhibited in vivo and in vitro the enzyme activity and that this inhibition was prevented by cysteamine and glutathione. The results suggest oxidation of essential sulfhydryl groups necessary for creatine kinase function by cystine. Considering that creatine kinase and other thiol-containing enzymes are crucial for renal energy metabolism, and programmed cell death occurs in situations of energy deficiency, the enzyme inhibition caused by cystine released from lysosomes might be a mechanism of tissue damage in patients with cystinosis.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Brazil.
authors.forename: Virginia Cielo
authors.initials: VC
authors.lastname: Rech
authors.forename: Genaro Azambuja
authors.initials: GA
authors.lastname: Athaydes
authors.forename: Luciane Rosa
authors.initials: LR
authors.lastname: Feksa
authors.forename: Paula Karine Barcelos
authors.initials: PK
authors.lastname: Dornelles
authors.forename: Valnes
authors.initials: V
authors.lastname: Rodrigues-Junior
authors.forename: Carlos Severo
authors.initials: CS
authors.lastname: Dutra-Filho
authors.forename: Angela Terezinha
authors.initials: AT
authors.lastname: De Souza Wyse
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
authors.forename: Clovis M D
authors.initials: CM
authors.lastname: Wannmacher
mesh_terms: D000367:Age Factors; D000818:Animals; D003402:Creatine Kinase / Q000037:antagonists & inhibitors*; D003553:Cystine / Q000633:toxicity*; D003554:Cystinosis / Q000201:enzymology / Q000209:etiology*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000378:metabolism
chemical_list: D013438:Sulfhydryl Compounds; D003553:Cystine; D003402:Creatine Kinase