Kessler Adriana, Costabeber Elisa, Dutra-Filho Carlos Severo, Wyse Angela Terezinha Souza, Wajner Moacir, Wannmacher Clóvis Milton Duval
Departamento de Bioquímica, Instituto de Ciências Básicas de Saúde, UFRGS, Porto Alegre, RS, Brazil.
Neurochem Res. 2003 Aug;28(8):1175-80. doi: 10.1023/a:1024220210380.
Type II hyperprolinemia is an inherited disorder caused by a deficiency of delta 1-pyrroline-5-carboxilic acid dehydrogenase, whose biochemical hallmark is proline accumulation in plasma and tissues. Although neurological symptoms occur in most patients, the neurotoxicity of proline is still controversial. The main objective of the present study was to investigate the effect of acute and chronic administration of proline on creatine kinase activity of brain cortex of 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 twice a day from the 6th to the 21st postpartum day. The results showed that creatine kinase activity was significantly inhibited in the brain cortex 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 cerebral cortex of 22-day-old nontreated rats. Proline significantly inhibited creatine kinase activity. Considering the importance of creatine kinase forthe 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.
II型高脯氨酸血症是一种由δ1-吡咯啉-5-羧酸脱氢酶缺乏引起的遗传性疾病，其生化特征是脯氨酸在血浆和组织中蓄积。尽管大多数患者会出现神经症状，但脯氨酸的神经毒性仍存在争议。本研究的主要目的是探讨急性和慢性给予脯氨酸对Wistar大鼠大脑皮层肌酸激酶活性的影响。急性处理是对22日龄大鼠皮下注射一次脯氨酸。对于慢性处理，从产后第6天至第21天每天给予脯氨酸两次。结果表明，急性给予脯氨酸的大鼠大脑皮层肌酸激酶活性显著受到抑制。相反，慢性给予脯氨酸的动物中该活性增加。我们还测定了脯氨酸对22日龄未处理大鼠大脑皮层肌酸激酶活性的体外作用。脯氨酸显著抑制了肌酸激酶活性。考虑到肌酸激酶对维持大脑能量稳态的重要性，可以想象大脑中这种酶活性的改变可能是脯氨酸具有神经毒性的机制之一。
