| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Outline of Final Research Achievements |
In this study, we found that ERp44, a factor involved in disulfide bond formation in the endoplasmic reticulum (ER), regulates angiotensin II. In mice, genetic loss of ERp44 destabilizes angiotensin II and causes hypotension. We found that ERp44 forms a mixed disulfide bond with ERAP1, an aminopeptidase that cleaves angiotensin II. ERp44 controls release of ERAP1 in a redox-dependent manner to control blood pressure. Additionally, we found that systemic inflammation triggers ERAP1 retention in the ER to inhibit hypotension. These results suggest that ERp44 redox-dependently regulates the intra- or extra-cellular localization of ERAP1, which contributes the control of serum angiotensin II level and blood pressure.
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