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
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
Externí odkaz: