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PAPP-A-Specific IGFBP-4 Proteolysis in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.
Adasheva, Daria A; Lebedeva, Olga S; Goliusova, Daria V; Postnikov, Alexander B; Teriakova, Maria V; Kopylova, Irina V; Lagarkova, Maria A; Katrukha, Alexey G; Serebryanaya, Daria V.
Afiliação
  • Adasheva DA; Department of Biochemistry, Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia.
  • Lebedeva OS; Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, Russia.
  • Goliusova DV; Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, Russia.
  • Postnikov AB; Hytest Ltd., 20520 Turku, Finland.
  • Teriakova MV; Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, Russia.
  • Kopylova IV; Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, Russia.
  • Lagarkova MA; Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, Russia.
  • Katrukha AG; Department of Biochemistry, Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia.
  • Serebryanaya DV; Hytest Ltd., 20520 Turku, Finland.
Int J Mol Sci ; 24(9)2023 May 08.
Article em En | MEDLINE | ID: mdl-37176126
The insulin-like growth factors IGF-I and IGF-II-as well as their binding proteins (IGFBPs), which regulate their bioavailability-are involved in many pathological and physiological processes in cardiac tissue. Pregnancy-associated plasma protein A (PAPP-A) is a metalloprotease that preferentially cleaves IGFBP-4, releasing IGF and activating its biological activity. Previous studies have shown that PAPP-A-specific IGFBP-4 proteolysis is involved in the pathogenesis of cardiovascular diseases, such as ischemia, heart failure, and acute coronary syndrome. However, it remains unclear whether PAPP-A-specific IGFBP-4 proteolysis participates in human normal cardiomyocytes. Here, we report PAPP-A-specific IGFBP-4 proteolysis occurring in human cardiomyocytes derived from two independent induced pluripotent cell lines (hiPSC-CMs), detected both on the cell surface and in the cell secretome. PAPP-A was measured by fluoroimmune analysis (FIA) in a conditioned medium of hiPSC-CMs and was detected in concentrations of up to 4.3 ± 1.33 ng/mL and 3.8 ± 1.1 ng/mL. The level of PAPP-A-specific IGFBP-4 proteolysis was determined as the concentration of NT-IGFBP-4 proteolytic fragments using FIA for a proteolytic neo-epitope-specific assay. We showed that PAPP-A-specific IGFBP-4 proteolysis is IGF-dependent and inhibited by EDTA and 1,10-phenanthroline. Therefore, it may be concluded that PAPP-A-specific IGFBP-4 proteolysis functions in human normal cardiomyocytes, and hiPSC-CMs contain membrane-bound and secreted forms of proteolytically active PAPP-A.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteína Plasmática A Associada à Gravidez / Células-Tronco Pluripotentes Induzidas Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteína Plasmática A Associada à Gravidez / Células-Tronco Pluripotentes Induzidas Idioma: En Ano de publicação: 2023 Tipo de documento: Article