Page 4 - H. Cell signaling

[H. Cell signaling-2]

p32-Dependent p38 MAPK Activation by Arginase II

Downregulation Contributes to Endothelial Nitric Oxide

Synthase Activation in HUVECs

Bon Hyeock Koo¹, Sung Woo Ryoo¹˙*

¹BIT medical-convergence, Kangwon national university, chun cheon 24341, Korea

Arginase II reciprocally regulates eNOS through a p32-dependent Ca2+ control. We investigated the signaling
pathway of arginase II-dependent eNOS phosphorylation. Western blot analysis was applied for examining protein
activation and [Ca2+]c was analyzed by microscopic and FACS analyses. NO and ROS productions were measured

using specific fluorescent dyes under microscopy. NO signaling pathway was tested by measuring vascular tension.
Following arginase II downregulation by chemical inhibition or gene knock out, increased eNOS phosphorylation

at Ser1177 and decreased phosphorylation at Thr495 was depend on p38 MAPK activation, which induced by
CaMKII activation through p32-dependent increase in [Ca2+]c. The protein amount of p32 negatively regulated p38

MAPK activation. p38 MAPK contributed to Akt-induced eNOS phosphorylation at Ser1177 that resulted in
accelerated NO production and reduced reactive oxygen species production in aortic endothelia. In vascular tension

assay, p38 MAPK inhibitor decreased acetylcholine-induced vasorelaxation responses and increased phenylephrine-
dependent vasoconstrictive responses. Here, we demonstrated a novel signaling pathway contributing to

understanding of the relationship between arginase II, endothelial dysfunction, and atherogenesis.