Chihiro Hisatsune and colleagues, RIKEN Brain Science Institute, Japan, have discovered a new mechanism for the regulation of blood pressure.
The team found that mice lacking the protein ERp44 had about 20 % lower than normal blood pressure. In these ERp44 knockout mice angiotensin II—a peptide hormone vital for maintaining blood pressure—was removed from circulation faster than in normal mice. This explains the drop in blood pressure. ERp44 is a multi-functional protein located in the endoplasmic reticulum (ER)—the place where proteins are folded into their proper shapes before being released into the rest of a cell. The enzyme ERAP1—an aminopeptidase which cleaves peptides like angiotensin—normally binds to ERp44 when the oxygen level inside of the ER is high. It is released into the blood when the oxygen level inside of the ER is low. Without any ERp44, all the ERAP1 was free to enter the blood stream where it digested angiotensin II. This lead to lower than normal blood pressure.
Current therapies for hypertension target the enzyme that produces angiotensin II. These results open the door to alternative approaches that target the activity of proteins like ERAP1 and ERp44.
- ERp44 exerts redox-dependent control of blood pressure at the ER,
Chihiro Hisatsune, Etsuko Ebisui, Masaya Usui, Naoko Ogawa, Akio Suzuki, Nobuko Mataga, Hiromi Takahashi-Iwanaga, and Katsuhiko Mikoshiba,
Molecular Cell 2015.
DOI: 10.1016/j.molcel.2015.04.008
