Page 6 - H. Cell signaling

[H. Cell signaling-3]

Hispidin, an extract of Phellinus Linteus, can alleviate

endothelial dysfunction by inhibiting arginase

Byeong Jun Yoon¹, Sung Woo Ryoo¹˙*

¹BIT Medical Convergence, Kangwon National University, Chun-cheon 24341, Korea

eNOS produces NO by using L-arginine as a substrate. NO produced by eNOS plays a key role in the maintenance
of vascular homeostasis. The reduction of NO production due to decrease of eNOS activity is considered an indicator
of almost all cardiovascular diseases. Arginase hydrolyzes L-arginine to L-ornithine, a precursor for spermine, which

has two isoforms for arginase, arginase l in the cytosol, and arginase ll in the mitochondria. In a recent study show

that arginase ll can regulate cytosolic Ca²+ level. As cytosolic Ca²+ levels are related eNOS activity, these results
suggest that arginase ll activity can modulate eNOS activity. Therefore, we studied whether arginase inhibition with
hispidin can alleviate endothelial dysfunction. First, hispidin effectively inhibited arginase, which induced

phosphorylation CaMKll thr286 and eNOS ser1177 residues in a Ca²+-dependent manner. The activity of eNOS
induced by cytosolic Ca²+ increased NO production, which increased acetylcholine response. However, the

contraction of phenylephrine was reduced. These effects were the same in ApoE-/- mice fed HCD, an arteriosclerosis
model, as well as in WT mice. In conclusion, hispidin can increase eNOS activity in a Ca²+-dependent manner, which

can alleviate endothelial dysfunction.