Effect of proline on creatine kinase activity in rat brain.
Type II Hyperprolinemia is an inherited disorder caused by a deficiency of delta1-pyrroline-5-carboxilic acid dehydrogenase, whose biochemical hallmark is proline accumulation in plasma and tissues. Although neurologic symptoms occur in most patients, the neurotoxicity of proline is still controversial. The main objective of this study was to investigate the effect of acute and chronic administration of proline on creatine kinase activity in the homogenates of cerebellum and midbrain from Wistar rats. Acute treatment was performed by subcutaneous administration of one injection of proline to 22-day-old rats. For chronic treatment, proline was administered four times a day from the 6th to the 21st postpartum day. The results showed that creatine kinase activity was significantly inhibited in the cerebellum and midbrain of rats subjected to acute proline administration. In contrast, this activity was increased in animals subjected to chronic administration. We also measured the in vitro effect of proline on creatine kinase activity in the same cerebral structures of 22-day-old nontreated rats. Proline significantly inhibited creatine kinase activity. Considering the importance of creatine kinase for the maintenance of energy homeostasis in the brain, it is conceivable that an alteration of this enzyme activity in the brain may be one of the mechanisms by which proline might be neurotoxic.
Kessler
Adriana
A
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil.
Costabeber
Elisa
E
Dutra-Filho
Carlos Severo
CS
Wyse
Angela Terezinha Souza
AT
Wajner
Moacir
M
Wannmacher
Clovis Milton Duval
CM
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002531:Cerebellum / Q000187:drug effects / Q000201:enzymology; D003402:Creatine Kinase / Q000378:metabolism*; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000201:enzymology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011392:Proline / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D009419:Nerve Tissue Proteins; D011392:Proline; D003402:Creatine Kinase