Federal Research Center "Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences", Institute of Cell Biophysics of the Russian Academy of Sciences, 142290 Pushchino, Russia.
Prokhorov General Physics Institute of the Russian Academy of Sciences, 38 Vavilove St., 119991 Moscow, Russia.
Int J Mol Sci. 2021 Dec 8;22(24):13216. doi: 10.3390/ijms222413216.
Ischemia-like (oxygen-glucose deprivation, OGD) conditions followed by reoxygenation (OGD/R) cause massive death of cerebral cortex cells in culture as a result of the induction of necrosis and apoptosis. Cell death occurs as a result of an OGD-induced increase in Ca ions in the cytosol of neurons and astrocytes, an increase in the expression of genes encoding proapoptotic and inflammatory genes with suppression of protective genes. The deuterated form of linoleic polyunsaturated fatty acid (D4-Lnn) completely inhibits necrosis and greatly reduces apoptotic cell death with an increase in the concentration of fatty acid in the medium. It was shown for the first time that D4-Lnn, through the activation of the phosphoinositide calcium system of astrocytes, causes their reactivation, which correlates with the general cytoprotective effect on the cortical neurons and astrocytes in vitro. The mechanism of the cytoprotective action of D4-Lnn involves the inhibition of the OGD-induced calcium ions, increase in the cytosolic and reactive oxygen species (ROS) overproduction, the enhancement of the expression of protective genes, and the suppression of damaging proteins.
类似缺血（氧葡萄糖剥夺，OGD）条件下再复氧（OGD/R）会导致培养的大脑皮层细胞大量死亡，这是由于坏死和细胞凋亡的诱导。细胞死亡是由于 OGD 诱导的神经元和星形胶质细胞胞质中钙离子增加，以及编码促凋亡和炎症基因的基因表达增加，同时抑制保护基因的表达所致。亚油酸多不饱和脂肪酸的氘代形式（D4-Lnn）完全抑制坏死，并随着脂肪酸浓度的增加大大减少细胞凋亡。首次表明，D4-Lnn 通过激活星形胶质细胞的磷酸肌醇钙系统，引起其再激活，这与体外对皮质神经元和星形胶质细胞的一般细胞保护作用相关。D4-Lnn 的细胞保护作用机制涉及抑制 OGD 诱导的钙离子、增加胞质和活性氧（ROS）的过度产生、增强保护基因的表达以及抑制破坏性蛋白质。
