Stanniocalcin-1 Protected Astrocytes from Hypoxic Damage Through the AMPK Pathway

• Published in: Neurochemical research Vol. 46; no. 11; pp. 2948 - 2957
• Main Authors: Sun, Binda, He, Shu, Liu, Bao, Xu, Gang, Guoji E, Feng, Lan, Xu, Licong, Chen, Dewei, Zhao, Wenqi, Chen, Jian, Gao, Yuqi, Zhang, Erlong
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-11-2021; Springer Nature B.V
• Subjects: AMP-Activated Protein Kinases - antagonists & inhibitors; AMP-Activated Protein Kinases - metabolism; Animal tissues; Animals; Apoptosis; Astrocytes; Astrocytes - metabolism; Astrocytes - pathology; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell Hypoxia - physiology; Cell Survival - physiology; Cell viability; Cells, Cultured; Cytoprotection - physiology; Damage; Gene Knockdown Techniques - methods; Glycolysis; Glycoproteins - biosynthesis; Homeostasis; Humans; Hypoxia; Hypoxia - metabolism; Hypoxia - prevention & control; Hypoxia-inducible factor 1a; Male; Mice; Mice, Inbred C57BL; Mitochondrial uncoupling protein 2; Neurochemistry; Neurology; Neurosciences; Original Paper; Oxidative stress; Stanniocalcin; Glycolysis; STC1; Hypoxia; AMPKα1; Astrocyte; Redox homeostasis
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-021-03393-z

Our previous studies revealed that the expression of stanniocalcin-1 (STC1) in astrocytes increased under hypoxic conditions. However, the role of STC1 in hypoxic astrocytes is not well understood. In this work, we first showed the increased expression of STC1 in astrocyte cell line and astrocytes in the brain tissues of mice after exposure to hypoxia. Then, we found that knockdown of STC1 inhibited cell viability and increased apoptosis. These effects were mediated by decreasing the levels of SIRT3, UCP2, and glycolytic genes and increasing the levels of ROS. Further studies suggested that STC1 silencing promoted oxidative stress and suppressed glycolysis by downregulating AMPKα1. Moreover, HIF-1α knockdown in hypoxic astrocytes led to decreased expression of STC1 and AMPKα1, indicating that the expression of STC1 was regulated by HIF-1α. In conclusion, our study showed that HIF-1α-induced STC1 could protect astrocytes from hypoxic damage by regulating glycolysis and redox homeostasis in an AMPKα1-dependent manner.