Abstract 11032: Peptide Lv Promotes the Trafficking and Membrane Insertion of Endothelial KCa31 Through the MEK1/ERK Pathway Academic Article uri icon


  • Background: Peptide Lv is an endogenous secretory peptide that is upregulated in the eyes of patients with diabetic retinopathy, an ocular disease with pathological angiogenesis. Peptide Lv promotes vascular endothelial cell proliferation, migration, and sprouting, and blocking peptide Lv with a specific antibody, anti-Lv, dampens neovascularization, so peptide Lv is an angiogenic factor. However, the molecular mechanism of how peptide Lv promotes angiogenesis is not clear. We found that peptide Lv causes endothelial cell membrane hyperpolarization, a step that is essential in endothelium-dependent angiogenesis. Peptide Lv augments the protein expression and current densities of K Ca 3.1, an ion channel underlying the endothelial hyperpolarization. As ion channels require trafficking and insertion to the plasma membrane to be functional after they are expressed, we aimed to determine the downstream signaling of peptide Lv that is involved in the trafficking of K Ca 3.1 in endothelial cells. Hypothesis: Peptide Lv activates the MEK1/ERK signaling pathway to promote the trafficking and membrane insertion of K Ca 3.1 in endothelial cells. Blocking MEK1/ERK will prevent augmentation of K Ca 3.1 by peptide Lv. Methods: Cultured human umbilical vein endothelial cells (HUVECs) were treated with peptide Lv (500 ng/ml) or PBS (vehicle control) in the presence/absence of FR180402 (10 M; an ERK inhibitor) or PD98059 (10 M, a MEK1 inhibitor) followed by the patch-clamp electrophysiological recordings and biotinylation assays. Results: Blocking ERK activation attenuated the peptide Lv-meditated membrane hyperpolarization and increase of K Ca 3.1 currents in endothelial cells. Blocking ERK activation did not affect peptide Lv-elicited increases of K Ca 3.1 protein expression, but it reduced the level of membrane-bound K Ca 3.1 Conclusions: The MEK1/ERK signaling pathway mediates peptide Lv-elicited trafficking and membrane insertion of K Ca 3.1 but does not affect the increase of K Ca 3.1 expression by peptide Lv.

published proceedings

  • Circulation

author list (cited authors)

  • Pham, D., Niemi, A., Blank, R., & Ko, G.

citation count

  • 0

complete list of authors

  • Pham, Dylan||Niemi, Autumn||Blank, Ria||Ko, Gladys

publication date

  • November 2022