Phospholipase D: A new mediator during high phosphate-induced vascular calcification associated with chronic kidney disease

Autor: Nader Hussein, Leyre Brizuela, Nicolas Vitale, Christophe O. Soulage, Najwa Skafi, Wissam H. Faour, Dina Abdallah, David Magne, Sophie Reibel, Bassam Badran, Eva Hamade, Saida Mebarek, René Buchet
Přispěvatelé: Métabolisme, Enzymes et Mécanismes Moléculaires (MEM²), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Physiologie intégrative, cellulaire et moléculaire (PICM), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Genomic and Health Laboratory, Genomic and Health Laboratory/PRASE-EDST, Plateforme d'hébergement et d'exploration fonctionnelle (Chronobiotron), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Lebanese University [Beirut] (LU), Lebanese University (LU), Lebanese National Council for Scientific Research (CNRS-L), Universite Claude Bernard Lyon 1
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
medicine.medical_specialty
Vascular smooth muscle
Phosphodiesterase Inhibitors
Physiology
[SDV]Life Sciences [q-bio]
Myocytes
Smooth Muscle
Clinical Biochemistry
chronic kidney disease (CKD)
Muscle
Smooth
Vascular
Cell Line
Rats
Sprague-Dawley
Tissue Culture Techniques
Mice
03 medical and health sciences
0302 clinical medicine
Internal medicine
Phospholipase D
medicine
Animals
Myocyte
Renal Insufficiency
Chronic
Vascular Calcification
vascular calcification (VC)
Protein kinase C
Mice
Knockout
phospholipase D (PLD)
Chemistry
PLD2
Cell Biology
Ascorbic acid
medicine.disease
3. Good health
Calcium
Dietary
Disease Models
Animal
030104 developmental biology
Endocrinology
030220 oncology & carcinogenesis
Cell Transdifferentiation
Phosphorus
Dietary
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Ex vivo
Signal Transduction
Calcification
Zdroj: Journal of Cellular Physiology
Journal of Cellular Physiology, Wiley, 2019, 234 (4), pp.4825--4839. ⟨10.1002/jcp.27281⟩
Journal of Cellular Physiology, Wiley, 2018
Journal of cellular physiology
Journal of cellular physiology, 2018
ISSN: 0021-9541
1097-4652
Popis: International audience; Vascular calcification (VC) is the pathological accumulation of calcium phosphate crystals in one of the layers of blood vessels, leading to loss of elasticity and causing severe calcification in vessels. Medial calcification is mostly seen in patients with chronic kidney disease (CKD) and diabetes. Identification of key enzymes and their actions during calcification will contribute to understand the onset of pathological calcification. Phospholipase D (PLD1, PLD2) is active at the earlier steps of mineralization in osteoblasts and chondrocytes. In this study, we aimed to determine their effects during high-phosphate treatment in mouse vascular smooth muscle cell line MOVAS, in the ex vivo model of the rat aorta, and in the in vivo model of adenine-induced CKD. We observed an early increase in PLD1 gene and protein expression along with the increase in the PLD activity in vascular muscle cell line, during calcification induced by ascorbic acid and beta-glycerophosphate. Inhibition of PLD1 by the selective inhibitor VU0155069, or the pan-PLD inhibitor, halopemide, prevented calcification. The mechanism of PLD activation is likely to be protein kinase C (PKC)-independent since bisindolylmaleimide X hydrochloride, a pan-PKC inhibitor, did not affect the PLD activity. In agreement, we found an increase in Pld1 gene expression and PLD activity in aortic explant cultures treated with high phosphate, whereas PLD inhibition by halopemide decreased calcification. Finally, an increase in both Pld1 and Pld2 expression occurred simultaneously with the appearance of VC in a rat model of CKD. Thus, PLD, especially PLD1, promotes VC in the context of CKD and could be an important target for preventing onset or progression of VC.
Databáze: OpenAIRE
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