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Expression and localization of calmodulin-related proteins in brain, heart and kidney from spontaneously hypertensive
Satoshi Kameshima1, Muneyoshi Okada1, Hideyuki Yamawaki1
1Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan.
Abstract:
Blood pressure is regulated not only by peripheral arterial resistance, but also by heart, kidney, and central nervous system. We have previously demonstrated that expression level of calmodulin-related proteins including eukaryotic elongation factor 2 kinase (eEF2K), death-associated protein kinase (DAPK)3, and histone deacetylase (HDAC)4 was specifically elevated in mesenteric artery from spontaneously hypertensive rats (SHR), which partly contributes to the development of hypertension via vascular inflammation and structural remodeling. We tested the hypothesis whether expression and localization of eEF2K, DAPK3, and HDAC4 are altered in brain, heart, and kidney from SHR. After brain, left ventricles (LV), and kidney were isolated from 12-week-old male Wistar Kyoto rats (WKY) and SHR, Western blotting and histological analysis were performed. In brain tissue, protein expression of eEF2K and HDAC4 was abundant, whereas DAPK3 protein was less. HDAC4 protein expression in SHR brain was significantly higher than that in WKY brain. In LV, protein expression of eEF2K was relatively higher than DAPK3 or HDAC4, and it was significantly higher in SHR than WKY. In kidney tissue, protein expression of DAPK3 was the highest and seemed to be localized specifically to renal tubule. The present results indicate that the increased HDAC4 in brain and increased eEF2K in LV might be at least in part related to the development of hypertension.
Insights
Hypertension involves calmodulin-related proteins. Increased histone deacetylase 4 (HDAC4) in the brain and eukaryotic elongation factor 2 kinase (eEF2K) in the heart may contribute to high blood pressure in spontaneously hypertensive rats.
Area of Science:
- Cardiovascular Physiology
- Molecular Biology
- Nephrology
Background:
- Blood pressure regulation involves multiple organs including the heart, kidney, and brain.
- Calmodulin-related proteins like eEF2K, DAPK3, and HDAC4 are implicated in hypertension development.
- Previous studies showed elevated eEF2K, DAPK3, and HDAC4 in mesenteric arteries of spontaneously hypertensive rats (SHR).
Purpose of the Study:
- To investigate the expression and localization of eEF2K, DAPK3, and HDAC4 in the brain, heart, and kidney of SHR.
- To determine if these proteins are altered in key organs involved in blood pressure regulation.
Main Methods:
- Western blotting and histological analysis were performed on brain, left ventricle (LV), and kidney tissues.
- Tissues were isolated from 12-week-old male Wistar Kyoto rats (WKY) and SHR.
Main Results:
- In SHR brains, HDAC4 protein expression was significantly higher than in WKY rats.
- In SHR left ventricles, eEF2K protein expression was significantly higher than in WKY rats.
- DAPK3 was most abundant in kidney tissue, localized to renal tubules.
Conclusions:
- Increased HDAC4 in the brain and increased eEF2K in the left ventricle may contribute to hypertension development.
- These findings highlight the role of specific calmodulin-related proteins in different organs during hypertension.
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