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Glucose up‐regulates HIF‐1α expression in primary cortical neurons in response to hypoxia through maintaining cellular redox status
Author(s) -
Guo Shuhong,
Bragina Olga,
Xu Yuexian,
Cao Zongxian,
Chen Hu,
Zhou Bo,
Morgan Marilee,
Lin Yong,
Jiang BingHua,
Liu Ke Jian,
Shi Honglian
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05287.x
Subject(s) - hypoxia (environmental) , microbiology and biotechnology , buthionine sulfoximine , reactive oxygen species , glutathione , ischemia , biology , biochemistry , chemistry , medicine , oxygen , organic chemistry , enzyme
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.