Department of Chemistry, Postgraduate Program in Toxicological Biochemistry, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Neurochem Res. 2013 Apr;38(4):886-94. doi: 10.1007/s11064-013-0994-3. Epub 2013 Feb 9.
It is well known that the levels of adenosine in the brain increase dramatically during cerebral hypoxic-ischemic (HI) insults. Its levels are tightly regulated by physiological and pathophysiological changes that occur during the injury acute phase. The aim of the present study was to examine the effects of the neonatal HI event on cytosolic and ecto-enzymes of purinergic system--NTPDase, 5'-nucleotidase (5'-NT) and adenosine deaminase (ADA)--in cerebral cortex of rats immediately post insult. Furthermore, the Na(+)/K(+)-ATPase activity, adenosine kinase (ADK) expression and thiobarbituric acid reactive species (TBARS) levels were assessed. Immediately after the HI event the cytosolic NTPDase and 5'-NT activities were increased in the cerebral cortex. In synaptosomes there was an increase in the ecto-ADA activity while the Na(+)/K(+) ATPase activity presented a decrease. The difference between ATP, ADP, AMP and adenosine degradation in synaptosomal and cytosolic fractions could indicate that NTPDase, 5'-NT and ADA were differently affected after insult. Interestingly, no alterations in the ADK expression were observed. Furthermore, the Na(+)/K(+)-ATPase activity was correlated negatively with the cytosolic NTPDase activity and TBARS content. The increased hydrolysis of nucleotides ATP, ADP and AMP in the cytosol could contribute to increased adenosine levels, which could be related to a possible innate neuroprotective mechanism aiming at potentiating the ambient levels of adenosine. Together, these results may help the understanding of the mechanism by which adenosine is produced following neonatal HI injury, therefore highlighting putative therapeutical targets to minimize ischemic injury and enhance recovery.
众所周知，在脑缺氧缺血（HI）损伤期间，大脑中的腺苷水平会急剧升高。其水平受到生理和病理生理变化的严格调节，这些变化发生在损伤急性期。本研究的目的是检查新生 HI 事件对大鼠大脑皮质中嘌呤能系统胞质和胞外酶-NTPDase、5'-核苷酸酶（5'-NT）和腺苷脱氨酶（ADA）的影响。此外，还评估了 Na(+)/K(+) -ATP 酶活性、腺苷激酶（ADK）表达和硫代巴比妥酸反应性物质（TBARS）水平。HI 事件后，大脑皮质中的胞质 NTPDase 和 5'-NT 活性立即增加。在突触体中，外源性 ADA 活性增加，而 Na(+)/K(+) -ATP 酶活性降低。突触体和胞质部分中 ATP、ADP、AMP 和腺苷降解之间的差异可能表明 NTPDase、5'-NT 和 ADA 在损伤后受到不同的影响。有趣的是，未观察到 ADK 表达的改变。此外，Na(+)/K(+) -ATP 酶活性与胞质 NTPDase 活性和 TBARS 含量呈负相关。胞质中核苷酸 ATP、ADP 和 AMP 的水解增加可能导致腺苷水平升高，这可能与增强环境中腺苷水平的潜在神经保护机制有关。总之，这些结果可能有助于理解新生 HI 损伤后腺苷产生的机制，从而突出潜在的治疗靶点，以最小化缺血性损伤并促进恢复。
