TRPC3-Nox2 axis mediates nutritional deficiency-induced cardiomyocyte atrophy
Autor: | Tomohiro Tanaka, Kazuhiro Nishiyama, Takuro Numaga-Tomita, Supachoke Mangmool, Motohiro Nishida, Sayaka Oda, Akiyuki Nishimura, Suhaini Binti Sudi, Caroline Sunggip |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Programmed cell death Cell Survival lcsh:Medicine Models Biological Article Contractility 03 medical and health sciences Adenosine Triphosphate 0302 clinical medicine Atrophy TRPC3 medicine Extracellular Animals Myocytes Cardiac lcsh:Science TRPC Cation Channels Heart Failure chemistry.chemical_classification Reactive oxygen species Multidisciplinary NADPH oxidase biology Malnutrition lcsh:R NADPH Oxidases medicine.disease Adenosine Rats Cell biology 030104 developmental biology chemistry NADPH Oxidase 2 biology.protein lcsh:Q Reactive Oxygen Species Biomarkers 030217 neurology & neurosurgery Signal Transduction medicine.drug |
Zdroj: | Scientific Reports, Vol 9, Iss 1, Pp 1-12 (2019) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | Myocardial atrophy, characterized by the decreases in size and contractility of cardiomyocytes, is caused by severe malnutrition and/or mechanical unloading. Extracellular adenosine 5′-triphosphate (ATP), known as a danger signal, is recognized to negatively regulate cell volume. However, it is obscure whether extracellular ATP contributes to cardiomyocyte atrophy. Here, we report that ATP induces atrophy of neonatal rat cardiomyocytes (NRCMs) without cell death through P2Y2 receptors. ATP led to overproduction of reactive oxygen species (ROS) through increased amount of NADPH oxidase (Nox) 2 proteins, due to increased physical interaction between Nox2 and canonical transient receptor potential 3 (TRPC3). This ATP-mediated formation of TRPC3-Nox2 complex was also pathophysiologically involved in nutritional deficiency-induced NRCM atrophy. Strikingly, knockdown of either TRPC3 or Nox2 suppressed nutritional deficiency-induced ATP release, as well as ROS production and NRCM atrophy. Taken together, we propose that TRPC3-Nox2 axis, activated by extracellular ATP, is the key component that mediates nutritional deficiency-induced cardiomyocyte atrophy. |
Databáze: | OpenAIRE |
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