Page 3 - H. Cell signaling

p32-Dependent p38 MAPK Activation by Arginase II Downregulation Contributes
to Endothelial Nitric Oxide Synthase Activation in HUVECs

Bon-hyeock Koo, Sungwoo Ryoo
Department of Biology, College of Natural Sciences, Kangwon National University, Chuncheon 200-701, Republic of Korea

BACKGROUND Methods

● p38 MAPK is an enzyme that is activated upon inhibition of arginase II in endothelial cells and
contributes to eNOS activity ● High cholesterol diet 4 weeks
● Our previous studies revealed that p32, is Ca 2+ regulator between mitochondria and cytosol, could be ● Western blotting analysis
regulated by arginase II activity.
● Mitochondrial fractionation
● In this study, we confirmed that mitochondrial p32 protein by inhibition of arginase II activity induces an
increase in cytosolic Ca 2+ and an increase in NO production by inducing activation of CaMKII-Akt- ● Confocal microscopy and flow cytometry
p38MAPK-eNOS signaling. ● Measurement of NO and ROS
● Thus, Repair of vascular function by arginase II down-regulation may be induced through activation of ● Aortic vascular tension assay
p38 MAPK and may occur through CaMKII-Akt-p38 MAPK-eNOS signaling pathway activity.
AIM
Therefore, arginase II regulated CaMKII-Akt-p38 MAPK-eNOS signaling pathway which
This study investigated that arginase II regulated CaMKII-Akt-p38 MAPK-eNOS signaling pathway which is
is important enzyme in vascular homeosis.
important enzyme cascade to maintaining vascular homeostasis.

RESULTS

Figure 2. Arginase II down-regulation increased cytosolic Ca 2+ level, which
phosphorylated p38 MAPK via activation of CaMKII
Figure 4. p38 MAPK activation through arginase II down-
regulation was regulated by Akt

Figure 5. Arginase II down-regulation increased NO production and
decrease ROS generation via eNOs activation, which was
Figure 1. Arginase II down-regulation induced to activate eNOS through Figure 3. p32 regulated phosphorylation of p38 MAPK. mediated by p38 MAPK.
p38 MAPK phosphorylation.

Figure 8. Although ApoE -/- + HCD model
could be repaired vascular function by
down-regulating arginase II, inhibition of
p38 MAPK disrupted endothelial dependent
vasorelaxation by decreasing NO
production
Figure 6. Arginase II down-regulation increased Ach dependent
vasorelaxation and decrease PE-dependent vasoconstriction by
activating p38 MAPK

Figure 7. ApoE -/- + HCD model decreased activity of eNOS compared
with WT and inhibition of p38 MAPK could reduce activation of eNOS.
CONCLUSION REFERENCES

● Arginase II down-regulation increased cytosolic Ca 2+ concentration by decreasing activity
of p32 which is Ca 2+ regulator between mitochondrial and cytosol. Koo BH et al. Arginase II inhibition prevents interleukin-8 production through
regulation of p38 MAPK phosphorylation activated by loss of mitochondrial
membrane potential in nLDL-stimulated hAoSMCs. Exp Mol Med. 2018 Feb 2.
● Increased cytosolic Ca 2+ level induced endothelial dependent vasorelaxation by activating
CaMKII-Akt-p38 MAPK-eNOS signaling cascade. Koo BH et al. Arginase II Contributes to the Ca 2+ /CaMKII/eNOS Axis by
Regulating Ca 2+ Concentration Between the Cytosol and Mitochondria in a
-/-
● Although ApoE + HCD model has reduced activity of CaMKII, Akt, p38 MAPK and eNOS p32-Dependent Manner. J Am Heart Assoc. 2018 Sep 18
compared WT, groups of down regulated arginase II recovered vascular function.