Increased phosphorylation of Ets-like transcription factor-1 in neurons of hypoxic preconditioned mice.

Ets-like transcription factor-1 (Elk-1) is a target of mitogen activated protein kinase (MAPK) which has been reported to play a key role in the induction of tolerance to ischemic and hypoxic injury, but little is known about the role of Elk-1 in the development of cerebral hypoxic preconditioning (HPC). In this study, we found that Elk-1 phosphorylation at Ser383 (p-Ser383 Elk-1), not protein expression, increased significantly (P < 0.05) in both hippocampus and frontal cortex of mice after repetitive auto-hypoxia exposures from 1 to 6 times (H1-H6, n = 6 for each group) when compared to that of the normoxic control group (H0, n = 6). The enhanced p-Ser383 Elk-1 was also found in the nuclear extract of H3 mice brain. Similarly, increased p-Ser383 Elk-1 was observed by immunostaining in the hippocampus and frontal cortex of mice from H3 and H6 groups. In addition, we found that the increased p-Ser383 Elk-1 co-localized with a neuron-specific protein, neurogranin, in the brain of H3 mice by using double immunofluorescence labeling. These results suggested that the enhanced neuron-specific phosphorylation of Elk-1 at Ser383 is involved in cerebral HPC of mice.