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The new insight into extracellular NAD+ degradation-the contribution of CD38 and CD73 in calcific aortic valve disease.
Jablonska, Patrycja; Kutryb-Zajac, Barbara; Mierzejewska, Paulina; Jasztal, Agnieszka; Bocian, Barbara; Lango, Romuald; Rogowski, Jan; Chlopicki, Stefan; Smolenski, Ryszard T; Slominska, Ewa M.
Affiliation
  • Jablonska P; Department of Biochemistry, Medical University of Gdansk, Gdansk, Poland.
  • Kutryb-Zajac B; Department of Biochemistry, Medical University of Gdansk, Gdansk, Poland.
  • Mierzejewska P; Department of Biochemistry, Medical University of Gdansk, Gdansk, Poland.
  • Jasztal A; Jagiellonian Center for Experimental Therapeutics, Jagiellonian University, Krakow, Poland.
  • Bocian B; Department of Cardiac & Vascular Surgery, Medical University of Gdansk, Gdansk, Poland.
  • Lango R; Department of Cardiac Anaesthesiology, Medical University of Gdansk, Gdansk, Poland.
  • Rogowski J; Department of Cardiac & Vascular Surgery, Medical University of Gdansk, Gdansk, Poland.
  • Chlopicki S; Jagiellonian Center for Experimental Therapeutics, Jagiellonian University, Krakow, Poland.
  • Smolenski RT; Department of Biochemistry, Medical University of Gdansk, Gdansk, Poland.
  • Slominska EM; Department of Biochemistry, Medical University of Gdansk, Gdansk, Poland.
J Cell Mol Med ; 2021 Jun 18.
Article in En | MEDLINE | ID: mdl-34142751
ABSTRACT
Nicotinamide adenine dinucleotide (NAD+ ) is crucial for cell energy metabolism and many signalling processes. Recently, we proved the role of ecto-enzymes in controlling adenine nucleotide-dependent pathways during calcific aortic valve disease (CAVD). This study aimed to investigate extracellular hydrolysis of NAD+ and mononucleotide nicotinamide (NMN) in aortic valves and aorta fragments of CAVD patients and on the inner aortic surface of ecto-5'-nucleotidase knockout mice (CD73-/-). Human non-stenotic valves (n = 10) actively converted NAD+ and NMN via both CD73 and NAD+ -glycohydrolase (CD38) according to our analysis with RP-HPLC and immunofluorescence. In stenotic valves (n = 50), due to reduced CD73 activity, NAD+ was degraded predominantly by CD38 and additionally by ALP and eNPP1. CAVD patients had significantly higher hydrolytic rates of NAD+ (0.81 ± 0.07 vs 0.56 ± 0.10) and NMN (1.12 ± 0.10 vs 0.71 ± 0.08 nmol/min/cm2 ) compared with controls. CD38 was also primarily engaged in human vascular NAD+ metabolism. Studies using specific ecto-enzyme inhibitors and CD73-/- mice confirmed that CD73 is not the only enzyme involved in NAD+ and NMN hydrolysis and that CD38 had a significant contribution to these pathways. Modifications of extracellular NAD+ and NMN metabolism in aortic valve cells may be particularly important in valve pathology and could be a potential therapeutic target.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: J Cell Mol Med Journal subject: BIOLOGIA MOLECULAR Year: 2021 Document type: Article Affiliation country: Poland

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: J Cell Mol Med Journal subject: BIOLOGIA MOLECULAR Year: 2021 Document type: Article Affiliation country: Poland