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β-arrestin2 Affects Cardiac Progenitor Cell Survival through Cell Mobility and Tube Formation in Severe Hypoxia.

β-arrestin2 Affects Cardiac Progenitor Cell Survival through Cell Mobility and Tube Formation in Severe Hypoxia.
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Seo SK, Kim N, Lee JH, Kim SM, Lee SY, Bae JW, Hwang KK, Kim DW, Koch WJ, Cho MC,


Seo SK, Kim N, Lee JH, Kim SM, Lee SY, Bae JW, Hwang KK, Kim DW, Koch WJ, Cho MC, (click to view)

Seo SK, Kim N, Lee JH, Kim SM, Lee SY, Bae JW, Hwang KK, Kim DW, Koch WJ, Cho MC,

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Korean circulation journal 48(4) 296-309 doi 10.4070/kcj.2017.0119
Abstract
BACKGROUND AND OBJECTIVES
β-arrestin2 (β-arr2) basically regulates multiple signaling pathways in mammalian cells by desensitization and internalization of G-protein coupled receptors (GPCRs). We investigated impacts of β-arr2 on survival, mobility, and tube formation of cardiac progenitor cells (CPCs) obtained from wild-type (WT) mouse (CPC-WT), and β-arr2 knock-out (KO) mouse (CPC-KO) cultured in presence or absence of serum and oxygen as non-canonical roles in GPCR system.

METHODS
CPCs were cultured in Dulbecco’s Modified Eagle Medium/Nutrient Mixture F-12 -based media containing fetal bovine serum and growth factors. Survival of 2 types of CPCs in hypoxia and/or serum deprivation was measured by fluorescence-activated cell sorting. Wound healing ability, and tube formation ability on Matrigel of 2 kinds of CPCs were compared in normoxic and hypoxic cultures. Protein expression related to survival and mobility were measured with the Western blot for each culture conditions.

RESULT
CPC-KO showed significantly worse mobility in the wound healing assay and in tube formation on Matrigel especially in hypoxic culture than did the CPC-WT. Also, CPC-KO showed significantly higher apoptosis fraction in both normoxic and hypoxic cultures than did the CPC-WT. Expression of proteins associated with cell survival and mobility, e.g., protein kinase B (Akt), β-catenin, and glycogen synthase kinase-3β (GSK-3β) was significantly worse in CPC-KO.

CONCLUSIONS
The CPC-KO had significantly worse cell mobility, tube formation ability, and survival than the CPC-WT, especially in the hypoxic cultures. Apparently, β-arr2 is important on CPC survival by means of mobility and tube formation in myocardial ischemia.

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