Discordant Tissue-Specific Expression of SAPK/MAPKJNK-Related Cofactors in Hypoxia and Hypoxia/Reoxygenation in a Model of Anoxia-Tolerance
Author: Haddad, John J.
Source: Protein and Peptide Letters, Volume 14, Number 4, April 2007 , pp. 373-380(8)
Publisher: Bentham Science Publishers
Abstract:Background: Pursuant to establishing the proteomic distribution of MAPKERK/MAPKp38 in the brain in a model of hypoxia-tolerance [Haddad, Protein Pept Lett, In press, 2007], I therein exclusively report the differential expression of MAPKJNK and related upstream and downstream kinases in various organs of the anoxia-tolerant turtle. Despite the fact that the aforementioned mechanisms involved dual expression of MAPKERK, the mechanistic distribution of MAPKJNK has not been previously unraveled. Changes in the phosphorylation state of MAPKs may occur during anoxia, thereby reversible protein phosphorylation could be a critical factor and major mechanism of metabolic reorganization for enduring anaerobiosis.
Methods: If a turtle were to undergo hypoxia akin to that experienced in its native habitat, it was placed in a glass aquarium filled with water to within a half inch of the top. After the turtle was anesthetized, through extended hypoxia or anesthesia, the animal was sacrificed by decapitation. The brain and other organs were then excised and placed in anoxic artificial cerebrospinal fluid. Total protein extraction was performed by homogenizing various organs in a suitable buffer, followed by determination of the phosphorylation states of SEK-1/MKK-4, SAPK/MAPKJNK and c-Jun activating protein (AP)-1.
Results: SEK-1/MKK-4 expression was mild in the cortex as compared with the manifold hypoxic (2h) induction in the liver. Continuous imposition of hypoxia (1 day - 1 week) increased the expression of SEK-1/MKK-4, thereafter declined at 3 weeks hypoxia. Hypoxia/reoxygenation weakly induced SEK-1/MKK-4 expression in cortex, in contrast with a strong induction in the liver, but not in other organs. Hypoxia (2h - 3 weeks) did not induce SAPK/MAPKJNK expression in cortex, despite prominent increase in liver, with mild reoxygenation effect. The normoxic induction of c-Jun AP-1 in cortex and rest of brain (ROB) was reduced with imposition of hypoxia (2h - 1 week). Furthermore, hypoxia (2h - 3 weeks) upregulated expression of c-Jun AP-1 in liver, heart and spleen, an effect abrogated with hypoxia/reoxygenation.
Conclusion: These results indicate that hypoxia differentially up-regulates the expression of MAPKJNK-related cofactors with organ-specific distribution. Since these modules are involved with neuroprotection in Chrysemys picta bellii, the expression of MAPKs bears relative mechanisms of specific responses to hypoxia tolerance.
Document Type: Research Article
Affiliations: Departments of Biology and Biomedical Sciences, Faculty of Arts and Sciences, Lebanese International University, Beirut 14-6404, Lebanon.
Publication date: April 2007
- Protein & Peptide Letters publishes short papers in all important aspects of protein and peptide research, including structural studies, recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, drug design etc. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallisation, and preliminary structure determinations of biologically important proteins are acceptable. Purely theoretical papers are also acceptable provided they provide new insight into the principles of protein/peptide structure and function.