The mechanism on phosphorylation of Hsp20Ser16 inhibit GA stress and ER stress during OGD/R

• DOI: 10.1371/journal.pone.0213410
• Publication Date: 2019-03-07T18:44:58Z
• Authors: Tonglin Lu; Yongyi Zou; Xu Zhou; Wenna Peng; Zhiping Hu
• Keywords: 0301 basic medicine; Science; Q; R; Golgi Apparatus; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Mitochondria; Oxygen; Mice; 03 medical and health sciences; Glucose; Cell Line, Tumor; Reperfusion Injury; Serine; Medicine; Animals; Humans; HSP20 Heat-Shock Proteins; Phosphorylation; Research Article

Recent research has demonstrated that small heat shock protein (sHsp) phosphorylation plays a variety of roles in neural cells. While the phosphorylation of serine 16 (Ser16) is blocked, Hsp20 no longer has neuroprotective effects. To further investigate the mechanism underlying this process, oxygen-glucose deprivation and reperfusion (OGD/R) was used with human SH-SY5Y cells and mouse N2a neuroblastoma cells. When SH-SY5Y and N2a cells were transfected with pEGFP-Hsp20(WT), pEGFP-Hsp20(S16A), and pEGFP-Hsp20(S16D) plasmids, the Golgi apparatus (GA) became more swollen and scattered, and many small fragments formed in the MOCK and S16A groups after OGD/R (P < 0.05). Meanwhile, the endoplasmic reticulum (ER) network was reduced, and the lamellar structure increased. However, these changes were not as obvious in the WT and S16D groups. Additionally, after OGD/R, Golgi Stress related protein contents were increased in the WT and S16D groups compared with the MOCK and S16A groups (P < 0.05). However, ER Stress related protein contents were decreased in the WT and S16D groups compared with the MOCK and S16A groups (P < 0.05). Our study demonstrates that Hsp20 phosphorylation on Ser16 protects against not only OGD/R-induced GA fragmentation in SH-SY5Y cells and N2a cells via Golgi stress but also OGD/R-induced ER structural changes in SH-SY5Y cells via ER stress. These findings suggest that Hsp20 is a potential drug target for ischemia stroke treatment.