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  • HMBOX1 interacts with MT2A to regulate autophagy and apoptosis in vascular endothelial cells.

HMBOX1 interacts with MT2A to regulate autophagy and apoptosis in vascular endothelial cells.

Scientific reports (2015-10-13)
HanLin Ma, Le Su, HongWei Yue, XiaoLei Yin, Jing Zhao, ShangLi Zhang, HsiangFu Kung, ZhiGang Xu, JunYing Miao
ABSTRACT

We previously found that Homeobox containing 1 (HMBOX1) was required for bone mesenchymal stem cell (BMSC) and mouse embryonic stem cell (ESC) differentiation into vascular endothelial cells (VECs). However, the function of HMBOX1 in VECs is still unknown. In this study, we found that HMBOX1 was abundantly expressed in the cytoplasm of human umbilical vascular endothelial cells (HUVECs). Knockdown of HMBOX1 induced apoptosis and inhibited autophagy. Overexpression of HMBOX1 inhibited apoptosis induced by fibroblast growth factor 2 deprivation and promoted autophagy. Metallothionein 2A (MT2A) was identified as an interaction protein with HMBOX1 by yeast two-hybrid assay, and confirmed by co-immunoprecipitation. Overexpression of HMBOX1 elevated intracellular free zinc level. Knockdown of MT2A inhibited this phenomenon. Moreover, N,N,N = ,N = -tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), a zinc chelator, reversed the anti-apoptosis and pro-autophagy effects of HMBOX1. In conclusion, HMBOX1 regulated intracellular free zinc level by interacting with MT2A to inhibit apoptosis and promote autophagy in VECs.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Monoclonal Anti-MT2A antibody produced in mouse, clone 6G2, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-β-Actin antibody produced in mouse, clone AC-15, ascites fluid
Sigma-Aldrich
MISSION® esiRNA, targeting human MT2A