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Globular CTRP3 promotes mitochondrial biogenesis in cardiomyocytes through AMPK/PGC-1α pathway.
Biochim Biophys Acta Gen Subj. 2017 Jan; 1861(1 Pt A):3085-3094.BB

Abstract

BACKGROUND

Mitochondrial biogenesis is crucial for the maintenance of mitochondrial function and cellular homeostasis. C1q/tumor necrosis factor-related protein-3 (CTRP3) is an adipokine that owns multiple functions on metabolic and cardiovascular diseases. However, whether CTRP3 affects mitochondrial biogenesis in cardiomyocytes remains unknown.

METHODS

Neonatal rat ventricular myocytes were cultured and treated with globular CTRP3 (gCTRP3). The expression of mitochondrial biogenesis related genes was measured by real-time PCR and western blot analysis. Mitochondrial morphology was assessed by a transmission electron microscope. ATP content, oxygen consumption rate (OCR), and sirtuin1 activity were measured with commercial kits.

RESULTS

gCTRP3 increased the expression of peroxisome proliferators activated receptor-γ co-activator-1α (PGC-1α), nuclear respiratory factor 1 (NRF-1), NRF-2, mitochondrial transcription factor A (TFAM), cytochrome B, and oxidative phosphorylation complexes III and V, and increased mitochondrial cristae components and OCR. Additionally, gCTRP3 enhanced mitochondrial DNA copy number and ATP content, while the induction was inhibited by knockdown of PGC-1α via small interfering RNA. gCTRP3 increased phosphorylation of AMP-activated protein kinase (AMPK), whereas adenine 9-β-d-arabinofuranoside (AraA), an AMPK inhibitor, attenuated gCTRP3-mediated induction of NRF-1, TFAM, and complexes III and V. gCTRP3 increased both the expression and activity of sirtuin1, whereas inhibition of sirtuin1 by EX-527 attenuated gCTRP3-induced responses. Meanwhile, gCTRP3-mediated activation of sirtuin1 was attenuated by AraA. Moreover, gCTRP3 restored the reduction of sirtuin1, PGC-1α, NRF-1, complex III and ATP content induced by hypoxia-reoxygenation injury.

CONCLUSION

CTRP3 promotes mitochondrial biogenesis in cardiomyocytes via AMPK/PGC-1α pathway.

GENERAL SIGNIFICANCE

CTRP3 is an endogenous modulator for mitochondrial biogenesis, and may protect cardiomyocytes by ameliorating mitochondrial dysfunction.

Authors+Show Affiliations

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, China.; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China.Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, China.; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China.Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, China.; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China.Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, China.; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China.Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, China.; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China.Department of Geriatrics, Peking University Third Hospital, Beijing 100191, China.Department of Geriatrics, Peking University Third Hospital, Beijing 100191, China.Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, China.; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China.. Electronic address: zhangy18@bjmu.edu.cn.Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, China.; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China.. Electronic address: pathophy@bjmu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27793739

Citation

Zhang, Cheng-Lin, et al. "Globular CTRP3 Promotes Mitochondrial Biogenesis in Cardiomyocytes Through AMPK/PGC-1α Pathway." Biochimica Et Biophysica Acta. General Subjects, vol. 1861, no. 1 Pt A, 2017, pp. 3085-3094.
Zhang CL, Feng H, Li L, et al. Globular CTRP3 promotes mitochondrial biogenesis in cardiomyocytes through AMPK/PGC-1α pathway. Biochim Biophys Acta Gen Subj. 2017;1861(1 Pt A):3085-3094.
Zhang, C. L., Feng, H., Li, L., Wang, J. Y., Wu, D., Hao, Y. T., Wang, Z., Zhang, Y., & Wu, L. L. (2017). Globular CTRP3 promotes mitochondrial biogenesis in cardiomyocytes through AMPK/PGC-1α pathway. Biochimica Et Biophysica Acta. General Subjects, 1861(1 Pt A), 3085-3094. https://doi.org/10.1016/j.bbagen.2016.10.022
Zhang CL, et al. Globular CTRP3 Promotes Mitochondrial Biogenesis in Cardiomyocytes Through AMPK/PGC-1α Pathway. Biochim Biophys Acta Gen Subj. 2017;1861(1 Pt A):3085-3094. PubMed PMID: 27793739.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Globular CTRP3 promotes mitochondrial biogenesis in cardiomyocytes through AMPK/PGC-1α pathway. AU - Zhang,Cheng-Lin, AU - Feng,Han, AU - Li,Li, AU - Wang,Jin-Yu, AU - Wu,Dan, AU - Hao,Yan-Ting, AU - Wang,Zheng, AU - Zhang,Yan, AU - Wu,Li-Ling, Y1 - 2016/10/26/ PY - 2016/07/25/received PY - 2016/10/19/revised PY - 2016/10/24/accepted PY - 2016/10/30/pubmed PY - 2017/11/4/medline PY - 2016/11/6/entrez KW - AMP-activated protein kinase KW - C1q/tumor necrosis factor-related protein-3 KW - Mitochondrial biogenesis KW - Peroxisome proliferators activated receptor-γ co-activator-1α KW - Sirtuin1 SP - 3085 EP - 3094 JF - Biochimica et biophysica acta. General subjects JO - Biochim Biophys Acta Gen Subj VL - 1861 IS - 1 Pt A N2 - BACKGROUND: Mitochondrial biogenesis is crucial for the maintenance of mitochondrial function and cellular homeostasis. C1q/tumor necrosis factor-related protein-3 (CTRP3) is an adipokine that owns multiple functions on metabolic and cardiovascular diseases. However, whether CTRP3 affects mitochondrial biogenesis in cardiomyocytes remains unknown. METHODS: Neonatal rat ventricular myocytes were cultured and treated with globular CTRP3 (gCTRP3). The expression of mitochondrial biogenesis related genes was measured by real-time PCR and western blot analysis. Mitochondrial morphology was assessed by a transmission electron microscope. ATP content, oxygen consumption rate (OCR), and sirtuin1 activity were measured with commercial kits. RESULTS: gCTRP3 increased the expression of peroxisome proliferators activated receptor-γ co-activator-1α (PGC-1α), nuclear respiratory factor 1 (NRF-1), NRF-2, mitochondrial transcription factor A (TFAM), cytochrome B, and oxidative phosphorylation complexes III and V, and increased mitochondrial cristae components and OCR. Additionally, gCTRP3 enhanced mitochondrial DNA copy number and ATP content, while the induction was inhibited by knockdown of PGC-1α via small interfering RNA. gCTRP3 increased phosphorylation of AMP-activated protein kinase (AMPK), whereas adenine 9-β-d-arabinofuranoside (AraA), an AMPK inhibitor, attenuated gCTRP3-mediated induction of NRF-1, TFAM, and complexes III and V. gCTRP3 increased both the expression and activity of sirtuin1, whereas inhibition of sirtuin1 by EX-527 attenuated gCTRP3-induced responses. Meanwhile, gCTRP3-mediated activation of sirtuin1 was attenuated by AraA. Moreover, gCTRP3 restored the reduction of sirtuin1, PGC-1α, NRF-1, complex III and ATP content induced by hypoxia-reoxygenation injury. CONCLUSION: CTRP3 promotes mitochondrial biogenesis in cardiomyocytes via AMPK/PGC-1α pathway. GENERAL SIGNIFICANCE: CTRP3 is an endogenous modulator for mitochondrial biogenesis, and may protect cardiomyocytes by ameliorating mitochondrial dysfunction. SN - 0304-4165 UR - https://www.unboundmedicine.com/medline/citation/27793739/Globular_CTRP3_promotes_mitochondrial_biogenesis_in_cardiomyocytes_through_AMPK/PGC_1α_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-4165(16)30398-1 DB - PRIME DP - Unbound Medicine ER -