Glucose up-regulates HIF-1 alpha expression in primary cortical neurons in response to hypoxia through maintaining cellular redox status |
| |
Authors: | Guo Shuhong Bragina Olga Xu Yuexian Cao Zongxian Chen Hu Zhou Bo Morgan Marilee Lin Yong Jiang Bing-Hua Liu Ke Jian Shi Honglian |
| |
Institution: | College of Pharmacy, University of New Mexico, Albuquerque, New Mexico, USA; School of Medicine, University of New Mexico, Albuquerque, New Mexico, USA; Mary Babb Randolph Cancer Center, and Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, Virginia, USA; Department of Neurosurgery, Second Affiliated Hospital of Zhejiang University, Hangzhou, China; The Neurogenetics Core, The Mind Research Network, Albuquerque, New Mexico, USA; Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA |
| |
Abstract: | It has been suggested that hypoxia-inducible factor 1 (HIF-1), a key regulator in cell's adaptation to hypoxia, plays an important role in the fate of neurons during ischemia. However, the mechanism of HIF-1 regulation is still not fully understood in neurons subjected to ischemia. In this study, we demonstrated that glucose up-regulated the expression of HIF-1α, the oxygen-dependent subunit of HIF-1, in rat primary cortical neurons exposed to hypoxia. To understand the mechanism of glucose-regulated HIF-1α expression, we investigated the relationships between HIF-1α expression, reactive oxygen species (ROS), and redox status. Low levels of HIF-1α protein expression were observed in the neurons exposed to in vitro ischemic conditions that had high levels of ROS (oxidizing environments), and vice versa . The glutathione (GSH) precursor, N -acetyl cysteine, induced HIF-1α protein expression in hypoxic neurons while the GSH synthesis inhibitor, l -buthionine sulfoximine, inhibited the expression. Moreover, (?)-epicatechin gallate, a ROS scavenger, elevated HIF-1α expression in the neurons subjected to in vitro ischemia. Furthermore, results from a systemic hypoxia model showed that a reducing environment increased HIF-1α expression in rat brains. Taken together, these data presented the first evidence that glucose promoted HIF-1α stabilization through regulating redox status in primary neurons exposed to hypoxia. The results imply that hypoxia only may not be sufficient to stabilize HIF-1α and that a reducing environment is required to stabilize HIF-1α in neurons exposed to hypoxia. |
| |
Keywords: | cerebral ischemia glucose hypoxia-inducible factor 1 primary neuron reactive oxygen species redox status |
本文献已被 PubMed 等数据库收录! |
|