Chemerin fragments show different effects on systemic blood pressure dependent on carboxyl-terminal cleavage site

Abstract

Chemerin is an adipocytokine whose concentration in blood correlates positively with blood pressure (BP). We have recently revealed that acute intracerebroventricular (i.c.v.) injection of chemerin-9, an active fragment of human chemerin, increased systemic BP in normal Wistar rats, suggesting that chemerin is involved in the central nervous control of peripheral BP. After secreted as an inactive form as prochemerin, a mature form of active chemerin is produced through the cleavage of its carboxyl (C)-terminus by proteases. Although the activity of cleaved products of chemerin has been extensively examined in vitro, in vivo effects remained to be elusive. In order to explore them, we performed acute i.c.v. injection of mouse chemerin-9 (mChemerin-9; 148F-156S), mouse chemerin-8 (mChemerin-8; 148F-155F), and mouse chemerin-7 (mChemerin-7; 148F-154A) into Wistar rats, and examined the effects on systemic BP. After chemerin fragment (1-30 nmol/head, i.c.v.) was cumulatively administered, systemic BP was measured by a cannulation method under an isoflurane anesthesia. mChemerin-9 but not mChemerin-8 and -7 induced a pressor response, which was concentration-dependent. In conclusion, we for the first time demonstrated that mChemerin-9 that corresponds to the C-terminal nine amino acids of active mouse chemerin156S increased systemic BP in rats, and also that chemerin fragments showed different effects on systemic BP dependent on how their C-terminus was cleaved.