TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice
Autor: | Yoshito Kumagai, Tsukasa Shimauchi, Akiyuki Nishimura, Sayaka Oda, Naoyuki Kitajima, Eri Harada, Lutz Birnbaumer, Takuro Numaga-Tomita, Tatsuya Ishikawa, Motohiro Nishida, Takashi Toyama |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Cardiac fibrosis TRPC6 purl.org/becyt/ford/1 [https] Mice CORAZON TRPC3 FIBROSIS Myocytes Cardiac Mice Knockout Multidisciplinary NADPH oxidase biology Lipid peroxide 3. Good health NADPH Oxidase 2 cardiovascular system Medicine CIENCIAS NATURALES Y EXACTAS medicine.drug Protein Binding Signal Transduction HIPERGLUCEMIA medicine.medical_specialty Lipid Peroxides Science Otras Ciencias Biológicas Primary Cell Culture Streptozocin Article Proinflammatory cytokine Diabetes Mellitus Experimental Ciencias Biológicas 03 medical and health sciences Internal medicine medicine TRPC6 Cation Channel Animals purl.org/becyt/ford/1.6 [https] TRPC Cation Channels Heart Failure 030102 biochemistry & molecular biology Myocardium TRPC3-Nox2 medicine.disease Streptozotocin Myocardial Contraction Rats 030104 developmental biology Endocrinology Gene Expression Regulation TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice 13. Climate action Heart failure Hyperglycemia biology.protein hyperglycemia Reactive Oxygen Species |
Zdroj: | Scientific Reports. 2017;7(1):1-14 CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET Scientific Reports Scientific Reports, Vol 7, Iss 1, Pp 1-14 (2017) Repositorio Institucional (UCA) Pontificia Universidad Católica Argentina instacron:UCA |
ISSN: | 2045-2322 |
Popis: | Fil: Oda, Sayaka. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; Japón Fil: Oda, Sayaka. The Graduate University for Advanced Studies. Department of Physiological Sciences; Japón Fil: Numaga-Tomita, Takuro. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; Japón Fil: Numaga-Tomita, Takuro. The Graduate University for Advanced Studies. Department of Physiological Sciences; Japón Fil: Kitajima, Naoyuki. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; Japón Fil: Kitajima, Naoyuki. Kyushu University. Graduate School of Pharmaceutical Sciences. Department of Translational Pharmaceutical Sciences; Japón Fil: Toyama, Takashi. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; Japón Fil: Toyama, Takashi. Kyushu University. Graduate School of Pharmaceutical Sciences. Department of Translational Pharmaceutical Sciences; Japón Fil: Toyama, Takashi. University of Tsukuba. Faculty of Medicine and Graduate School of Comprehensive Human Sciences. Environmental Biology Laboratory; Japón Fil: Harada, Eri. Ajinomoto Company Incorporated; Japón Fil: Harada, Eri. EA Pharma Company; Japón Fil: Shimauchi, Tsukasa. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; Japón Fil: Shimauchi, Tsukasa. Kyushu University. Graduate School of Pharmaceutical Sciences. Department of Translational Pharmaceutical Sciences; Japón Fil: Nishimura, Akiyuki. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; Japón Fil: Nishimura, Akiyuki. The Graduate University for Advanced Studies. Department of Physiological Sciences; Japón Fil: Ishikawa, Tatsuya. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; Japón Fil: Ishikawa, Tatsuya. Kyushu University. Graduate School of Pharmaceutical Sciences. Department of Translational Pharmaceutical Sciences; Japón Fil: Ishikawa, Tatsuya. EA Pharma Company; Japón Fil: Kumagai, Yoshito. University of Tsukuba. Faculty of Medicine and Graduate School of Comprehensive Human Sciences. Environmental Biology Laboratory; Japón Fil: Birnbaumer, Lutz. National Institute of Environmental Health Sciences. Laboratory of Neuroscience; Estados Unidos Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina Fil: Nishida, Motohiro. National Institute for Physiological Sciences. Division of Cardiocirculatory Signaling; Japón Fil: Nishida, Motohiro. The Graduate University for Advanced Studies. Department of Physiological Sciences; Japón Fil: Kyushu University. Graduate School of Pharmaceutical Sciences. Department of Translational Pharmaceutical Sciences; Japón Abstract: Excess production of reactive oxygen species (ROS) caused by hyperglycemia is a major risk factor for heart failure. We previously reported that transient receptor potential canonical 3 (TRPC3) channel mediates pressure overload-induced maladaptive cardiac fibrosis by forming stably functional complex with NADPH oxidase 2 (Nox2). Although TRPC3 has been long suggested to form hetero-multimer channels with TRPC6 and function as diacylglycerol-activated cation channels coordinately, the role of TRPC6 in heart is still obscure. We here demonstrated that deletion of TRPC6 had no impact on pressure overload-induced heart failure despite inhibiting interstitial fibrosis in mice. TRPC6-deficient mouse hearts 1 week after transverse aortic constriction showed comparable increases in fibrotic gene expressions and ROS production but promoted inductions of inflammatory cytokines, compared to wild type hearts. Treatment of TRPC6-deficient mice with streptozotocin caused severe reduction of cardiac contractility with enhancing urinary and cardiac lipid peroxide levels, compared to wild type and TRPC3-deficient mice. Knockdown of TRPC6, but not TRPC3, enhanced basal expression levels of cytokines in rat cardiomyocytes. TRPC6 could interact with Nox2, but the abundance of TRPC6 was inversely correlated with that of Nox2. These results strongly suggest that Nox2 destabilization through disrupting TRPC3-Nox2 complex underlies attenuation of hyperglycemia-induced heart failure by TRPC6. |
Databáze: | OpenAIRE |
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