The Temporal and Spatial Changes of Autophagy and PI3K Isoforms in Different Neural Cells After Hypoxia/Reoxygenation Injury.

ABSTRACT

There are limited therapeutic options for patient with traumatic spinal cord injury (SCI). Phosphoinositide 3-kinase family (PI3Ks) are the key molecules for regulating cell autophagy, which is a possible way of treating SCI. As we know, PI3K family are composed of eight isoforms, which are distributed into three classes. While the role of PI3Ks in regulating autophagy is controversial and the effects may be in a cell-specific manner. Different isoforms do not distribute in neural cells consistently and it is not clear how the PI3K isoforms regulate and interact with autophagy. Therefore, we explored the distributions and expression of different PI3K isoforms in two key neural cells (PC12 cells and astrocytes). The results showed that the expression of LC3II/I and p62, which are the markers of autophagy, changed in different patterns in PC12 cells and astrocytes after hypoxia/reoxygenation injury (H/R). Furthermore, the mRNA level of eight PI3K isoforms did not change in the same way, and even for the same isoform the mRNA activities are different between PC12 cells and astrocytes. What is more, the results of western blot of PI3K isoforms after H/R were inconsistent with the relevant mRNA. Based on this study, the therapeutic effects of regulating autophagy on SCI are not confirmed definitely, and its molecular mechanisms may be related with different temporal and spatial patterns of activation and distributions of PI3K isoforms.