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Decreased phosphorylation and protein expression of ERK1/2 in the brain of hypoxic preconditioned mice
Caixia Long1, Yanan Gao, Ge Gao
1Institute for Biomedical Science of Pain, Beijing Key Laboratory for Neural Regeneration and Repairing, Department of Neurobiology, Capital University of Medical Sciences, #10 You An Men Wai Xi Tou Tiao, Beijing 100054, China.
Abstract:
Accumulated reports have suggested that activation of protein kinase C (PKC) isoforms may involve the activation of extracellular signal-regulated kinases 1/2 (ERK1/2) in the neuronal response to hypoxic stimuli. We have previously demonstrated that the membrane translocation or activation of conventional PKC (cPKC) betaII, gamma and novel PKC (nPKC) epsilon are increased in the early phase of cerebral hypoxic preconditioning in mice. However, the role of ERK1/2 in the development of cerebral hypoxic preconditioning is unclear. In the current study, we used Western blot analysis to investigate the effects of repetitive hypoxic exposure (H0-H6, n=6 for each group) on the levels of phosphorylation and protein expression of ERK1/2 in the frontal cortex and the whole hippocampus of mice. We found that the levels of phosphorylated ERK1/2, not protein expression of ERK1/2, decreased significantly in both cortex and hippocampus of the early hypoxic preconditioned mice (H1-H4), when compared to that of the normoxic group (p<0.05). In addition, a significant decrease (p<0.05) in the ERK1/2 protein expression, not the phosphorylated form of ERK1/2, was found both in the frontal cortex and hippocampus of mice followed hypoxia with previous hypoxia (H5 and H6). These results suggest that the decreased phosphorylation and downregulation of protein expression of ERK1/2 might be involved in the development of hypoxic preconditioning.
Insights
Decreased extracellular signal-regulated kinases 1/2 (ERK1/2) phosphorylation and expression are linked to hypoxic preconditioning in mice brains. This suggests a role for ERK1/2 downregulation in developing brain protection against hypoxia.
Area of Science:
- Neuroscience
- Cellular Biology
- Biochemistry
Background:
- Protein kinase C (PKC) activation may involve extracellular signal-regulated kinases 1/2 (ERK1/2) in neuronal responses to hypoxia.
- Previous studies showed increased conventional PKC (cPKC) and novel PKC (nPKC) activation during early cerebral hypoxic preconditioning in mice.
Purpose of the Study:
- To investigate the role of ERK1/2 in the development of cerebral hypoxic preconditioning.
- To examine the effects of repetitive hypoxic exposure on ERK1/2 phosphorylation and protein expression in mouse brain.
Main Methods:
- Western blot analysis was used to assess ERK1/2 phosphorylation and protein levels.
- Mice were subjected to repetitive hypoxic exposure (H0-H6).
- Analyses were conducted on frontal cortex and hippocampus tissues.
Main Results:
- Phosphorylated ERK1/2 levels significantly decreased in both cortex and hippocampus during early hypoxic preconditioning (H1-H4).
- ERK1/2 protein expression significantly decreased in both brain regions in mice with prior hypoxia exposure (H5 and H6).
- No significant changes were observed in protein expression for phosphorylated ERK1/2, or vice versa for total ERK1/2.
Conclusions:
- Decreased ERK1/2 phosphorylation may be involved in the early stages of hypoxic preconditioning.
- Downregulation of ERK1/2 protein expression might play a role in the sustained development of hypoxic preconditioning.
- These findings suggest a complex regulatory role for ERK1/2 signaling in cerebral hypoxic adaptation.
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