Mateos Melina V, Giusto Norma M, Salvador Gabriela A
Instituto de Investigaciones Bioquímicas de Bahía Blanca, Universidad Nacional del Sur and Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina.
Biochim Biophys Acta. 2012 Dec;1823(12):2136-48. doi: 10.1016/j.bbamcr.2012.09.005. Epub 2012 Sep 23.
The role of iron in oxidative injury in the nervous system has been extensively described. However, little is known about the role of lipid signal transduction in neurodegeneration processes triggered by iron overload. The purpose of this work was to characterize the regulation and the crosstalk between phosphatidylcholine (PC)-derived diacylglycerol (DAG) and cannonical signaling pathways during iron-induced oxidative stress in cerebral cortex synaptic endings (Syn) obtained from adult (4 months old) and aged (28 months old) rats. DAG production was increased in Syn exposed to iron. This rise in DAG formation was due to phospholipase D1 (PLD1) and PLD2 activations. In adult rats, PKD1, ERK1/2 and PKCα/βII activations were PLD1 and PLD2 dependent. In contrast, in senile rats, DAG formation catalyzed by PLDs did not participate in PKD1, ERK1/2 and PKCα/βII regulations, but it was dependent on ERK and PKC activities. Iron-induced oxidative stress promoted an increased localization of PLD1 in membrane rafts, whereas PLD2 was excluded from these domains and appeared to be involved in glutamate transporter function. Our results show a differential regulation and synaptic function of DAG generated by PLDs during iron-induced oxidative stress as a consequence of aging.
铁在神经系统氧化损伤中的作用已被广泛描述。然而，关于脂质信号转导在铁过载引发的神经退行性变过程中的作用却知之甚少。本研究的目的是表征成年（4个月大）和老年（28个月大）大鼠大脑皮质突触末梢（Syn）在铁诱导的氧化应激过程中，磷脂酰胆碱（PC）衍生的二酰基甘油（DAG）与经典信号通路之间的调控及相互作用。暴露于铁的Syn中DAG生成增加。DAG形成的这种增加归因于磷脂酶D1（PLD1）和磷脂酶D2（PLD2）的激活。在成年大鼠中，蛋白激酶D1（PKD1）、细胞外信号调节激酶1/2（ERK1/2）和蛋白激酶Cα/βII（PKCα/βII）的激活依赖于PLD1和PLD2。相反，在老年大鼠中，由PLD催化的DAG形成不参与PKD1、ERK1/2和PKCα/βII的调控，但依赖于ERK和PKC的活性。铁诱导的氧化应激促进了PLD1在膜筏中的定位增加，而PLD2被排除在这些区域之外，似乎参与了谷氨酸转运体功能。我们的结果表明，衰老导致铁诱导的氧化应激过程中，PLD产生的DAG存在差异调控和突触功能。
