8 results on '"Danyang Chong"'
Search Results
2. Neonatal ketone body elevation regulates postnatal heart development by promoting cardiomyocyte mitochondrial maturation and metabolic reprogramming
- Author
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Danyang Chong, Yayun Gu, Tongyu Zhang, Yu Xu, Dandan Bu, Zhong Chen, Na Xu, Liangkui Li, Xiyu Zhu, Haiquan Wang, Yangqing Li, Feng Zheng, Dongjin Wang, Peng Li, Li Xu, Zhibin Hu, and Chaojun Li
- Subjects
Cytology ,QH573-671 - Abstract
Abstract Neonatal heart undergoes metabolic conversion and cell cycle arrest preparing for the increased workload during adulthood. Herein, we report that neonatal ketone body elevation is a critical regulatory factor for postnatal heart development. Through multiomics screening, we found that the expression of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), the rate-limiting enzyme of ketogenesis, was transiently induced by colostrum in the neonatal heart. Hmgcs2 knockout caused mitochondrial maturation defects. Meanwhile, postnatal heart development was compromised and cardiomyocytes reacquired proliferation capacity in Hmgcs2 knockout mice. Consequently, over 40% of newborn Hmgcs2 knockout mice died before weaning. The heart function of surviving Hmgcs2 knockout mice was also impaired, which could be rescued by ketone body supplementation during the suckling stage. Mechanistically, ketone body deficiency inhibited β-hydroxybutyrylation but enhanced acetylation of mitochondrial proteins, which might be responsible for the inhibition of the enzyme activity in mitochondria. These observations suggest that ketone body is critical for postnatal heart development through regulating mitochondrial maturation and metabolic reprogramming.
- Published
- 2022
- Full Text
- View/download PDF
3. Neonatal ketone body elevation regulates postnatal heart development by promoting cardiomyocyte mitochondrial maturation and metabolic reprogramming
- Author
-
Danyang Chong, Yayun Gu, Tongyu Zhang, Yu Xu, Dandan Bu, Zhong Chen, Na Xu, Liangkui Li, Xiyu Zhu, Haiquan Wang, Yangqing Li, Feng Zheng, Dongjin Wang, Peng Li, Li Xu, Zhibin Hu, and Chaojun Li
- Subjects
Genetics ,Cell Biology ,Molecular Biology ,Biochemistry - Abstract
Neonatal heart undergoes metabolic conversion and cell cycle arrest preparing for the increased workload during adulthood. Herein, we report that neonatal ketone body elevation is a critical regulatory factor for postnatal heart development. Through multiomics screening, we found that the expression of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), the rate-limiting enzyme of ketogenesis, was transiently induced by colostrum in the neonatal heart. Hmgcs2 knockout caused mitochondrial maturation defects. Meanwhile, postnatal heart development was compromised and cardiomyocytes reacquired proliferation capacity in Hmgcs2 knockout mice. Consequently, over 40% of newborn Hmgcs2 knockout mice died before weaning. The heart function of surviving Hmgcs2 knockout mice was also impaired, which could be rescued by ketone body supplementation during the suckling stage. Mechanistically, ketone body deficiency inhibited β-hydroxybutyrylation but enhanced acetylation of mitochondrial proteins, which might be responsible for the inhibition of the enzyme activity in mitochondria. These observations suggest that ketone body is critical for postnatal heart development through regulating mitochondrial maturation and metabolic reprogramming.
- Published
- 2021
4. Geranylgeranyl pyrophosphate-mediated protein geranylgeranylation regulates endothelial cell proliferation and apoptosis during vasculogenesis in mouse embryo
- Author
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Shan Guan, Na Xu, Chao-Jun Li, Tongyu Zhang, Danyang Chong, Yue Zhao, and Zhong Chen
- Subjects
RHOA ,Geranylgeranyl pyrophosphate ,Protein Prenylation ,Embryonic Development ,Apoptosis ,Biology ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Vasculogenesis ,Geranylgeraniol ,Polyisoprenyl Phosphates ,Multienzyme Complexes ,Pregnancy ,Genetics ,Morphogenesis ,Animals ,Farnesyltranstransferase ,Molecular Biology ,030304 developmental biology ,Cell Proliferation ,0303 health sciences ,Cell growth ,Endothelial Cells ,Cell Differentiation ,YAP-Signaling Proteins ,Embryo, Mammalian ,Embryonic stem cell ,Cell biology ,Endothelial stem cell ,chemistry ,biology.protein ,Female ,Mevalonate pathway ,rhoA GTP-Binding Protein ,030217 neurology & neurosurgery - Abstract
Vascular development is essential for the establishment of the circulatory system during embryonic development and requires the proliferation of endothelial cells. However, the underpinning regulatory mechanisms are not well understood. Here, we report that geranylgeranyl pyrophosphate (GGPP), a metabolite involved in protein geranylgeranylation, plays an indispensable role in embryonic vascular development. GGPP is synthesized by geranylgeranyl pyrophosphate synthase (GGPPS) in the mevalonate pathway. The selective knockout of Ggpps in endothelial cells led to aberrant vascular development and embryonic lethality, resulting from the decreased proliferation and enhanced apoptosis of endothelial cells during vasculogenesis. The defect in protein geranylgeranylation induced by GGPP depletion inhibited the membrane localization of RhoA and enhanced yes-associated protein (YAP) phosphorylation, thereby prohibiting the entry of YAP into the nucleus and the expression of YAP target genes related to cell proliferation and the antiapoptosis process. Moreover, inhibition of the mevalonate pathway by simvastatin induced endothelial cell proliferation defects and apoptosis, which were ameliorated by GGPP. Geranylgeraniol (GGOH), a precursor of GGPP, ameliorated the harmful effects of simvastatin on vascular development of developing fetuses in pregnant mice. These results indicate that GGPP-mediated protein geranylgeranylation is essential for endothelial cell proliferation and the antiapoptosis process during embryonic vascular development.
- Published
- 2020
5. GGPP depletion initiates metaflammation through disequilibrating CYB5R3-dependent eicosanoid metabolism
- Author
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Tao Tao, Xin Chen, Zhihui Jiang, Yongjuan Sang, Jie Sun, Wei Zhao, Chao-Jun Li, Danyang Chong, Lisha Wei, Pei Wang, Min-Sheng Zhu, Tiantian Qiu, Xuena Zhang, Yan-Yan Zheng, Ye Wang, Yeqiong Li, and Yuwei Zhou
- Subjects
0301 basic medicine ,Simvastatin ,Geranylgeranyl pyrophosphate ,Mevalonic Acid ,Inflammation ,Endoplasmic Reticulum ,Biochemistry ,Proinflammatory cytokine ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,Prenylation ,Polyisoprenyl Phosphates ,medicine ,Animals ,Molecular Biology ,Mice, Knockout ,030102 biochemistry & molecular biology ,Eicosanoid metabolism ,Chemistry ,Lipid signaling ,Cell Biology ,Cell biology ,Mitochondria ,Protein Transport ,030104 developmental biology ,Eicosanoid ,Eicosanoids ,lipids (amino acids, peptides, and proteins) ,Mevalonate pathway ,medicine.symptom ,Cytochrome-B(5) Reductase - Abstract
Metaflammation is a primary inflammatory complication of metabolic disorders characterized by altered production of many inflammatory cytokines, adipokines, and lipid mediators. Whereas multiple inflammation networks have been identified, the mechanisms by which metaflammation is initiated have long been controversial. As the mevalonate pathway (MVA) produces abundant bioactive isoprenoids and abnormal MVA has a phenotypic association with inflammation/immunity, we speculate that isoprenoids from the MVA may provide a causal link between metaflammation and metabolic disorders. Using a line with the MVA isoprenoid producer geranylgeranyl diphosphate synthase (GGPPS) deleted, we find that geranylgeranyl pyrophosphate (GGPP) depletion causes an apparent metaflammation as evidenced by abnormal accumulation of fatty acids, eicosanoid intermediates, and proinflammatory cytokines. We also find that GGPP prenylate cytochrome b(5) reductase 3 (CYB5R3) and the prenylated CYB5R3 then translocate from the mitochondrial to the endoplasmic reticulum (ER) pool. As CYB5R3 is a critical NADH-dependent reductase necessary for eicosanoid metabolism in ER, we thus suggest that GGPP-mediated CYB5R3 prenylation is necessary for metabolism. In addition, we observe that pharmacological inhibition of the MVA pathway by simvastatin is sufficient to inhibit CYB5R3 translocation and induces smooth muscle death. Therefore, we conclude that the dysregulation of MVA intermediates is an essential mechanism for metaflammation initiation, in which the imbalanced production of eicosanoid intermediates in the ER serve as an important pathogenic factor. Moreover, the interplay of MVA and eicosanoid metabolism as we reported here illustrates a model for the coordinating regulation among metabolite pathways.
- Published
- 2020
6. Geranylgeranyl pyrophosphate synthase facilitates the organization of cardiomyocytes during mid-gestation through modulating protein geranylgeranylation in mouse heart
- Author
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Chen Jiang, Zhongzhou Yang, Chao-Jun Li, Zhong Chen, Shan Guan, Danyang Chong, and Na Xu
- Subjects
0301 basic medicine ,rho GTP-Binding Proteins ,Geranylgeranyl pyrophosphate ,Genotype ,Physiology ,Transgene ,Protein Prenylation ,Gestational Age ,Mice, Transgenic ,03 medical and health sciences ,chemistry.chemical_compound ,Geranylgeranylation ,Fetal Heart ,Multienzyme Complexes ,Pregnancy ,Physiology (medical) ,Morphogenesis ,Myocyte ,Animals ,Farnesyltranstransferase ,Humans ,Myocytes, Cardiac ,Regulation of gene expression ,Embryonic heart ,Chemistry ,Gene Expression Regulation, Developmental ,Cell biology ,body regions ,Mice, Inbred C57BL ,030104 developmental biology ,Intercellular Junctions ,Phenotype ,cardiovascular system ,Homeobox Protein Nkx-2.5 ,Protein prenylation ,Female ,Signal transduction ,Cardiology and Cardiovascular Medicine ,HeLa Cells ,Signal Transduction - Abstract
Aims With the maturation of placenta, ventricular chamber maturation enhances cardiac contractile performance to adapt to the metabolic demand of growing embryo. The organization of cardiomyocytes is required for the morphological remodelling in ventricular chamber maturation. However, the mechanism governing the establishment of cardiac cytoarchitecture during ventricular chamber maturation is still poorly studied. Methods and results Here, we found that the expression of geranylgeranyl pyrophosphate synthase (Ggpps), which mediates protein geranylgeranylation, increased in the mouse heart after the onset of placental function. By using different Cre lines, we found that the cardiac inactivation of Ggpps by the Nkx2.5Cre/+ line disrupted protein geranylgeranylation as early as E9.5, which affected ventricular chamber maturation and resulted in mid-gestational embryonic lethality. In contrast, α-SMA-Cre line mediated the disruption of protein geranylgeranylation from E13.5 did not affect embryonic heart development. Further analysis of Nkx2.5Cre/+; Ggppsfl/fl mutants showed that the loss of Ggpps caused disorganized cardiac cytoarchitecture as early as E11.5 by disturbing cell-cell junctions. Ggpps inactivation decreased Rho GTPase geranylgeranylation and their activity, which might account for the disruption of cell-cell junctions. Moreover, elevating the protein geranylgeranylation by supplement of geranylgeranyl pyrophosphate (GGPP) could recover the Ggpps deficient induced defects of cytoarchitecture and cell-cell junctions in vitro and in vivo. Conclusion Our present study demonstrates that GGPPS-mediated protein geranylgeranylation plays an indispensable role in the ventricular chamber maturation and acts as a stage-specific signal to regulate the establishment of cardiac cytoarchitecture during mid-gestation.
- Published
- 2017
7. Geranylgeranyl pyrophosphate synthase facilitates the organization of cardiomyocytes during mid-gestation through modulating protein geranylgeranylation in mouse heart.
- Author
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Zhong Chen, Na Xu, Danyang Chong, Shan Guan, Chen Jiang, Zhongzhou Yang, and Chaojun Li
- Subjects
PYROPHOSPHATES ,HEART cells ,EMBRYOLOGY ,HEART histology ,LABORATORY mice ,PHYSIOLOGY - Abstract
Aims With the maturation of placenta, ventricular chamber maturation enhances cardiac contractile performance to adapt to the metabolic demand of growing embryo. The organization of cardiomyocytes is required for the morphological remodelling in ventricular chamber maturation. However, the mechanism governing the establishment of cardiac cytoarchitecture during ventricular chamber maturation is still poorly studied. Methods and results Here, we found that the expression of geranylgeranyl pyrophosphate synthase (Ggpps), which mediates protein geranylgeranylation, increased in the mouse heart after the onset of placental function. By using different Cre lines, we found that the cardiac inactivation of Ggpps by the Nkx2.5
Cre/+ line disrupted protein geranylgeranylation as early as E9.5, which affected ventricular chamber maturation and resulted in mid-gestational embryonic lethality. In contrast, a-SMA-Cre line mediated the disruption of protein geranylgeranylation from E13.5 did not affect embryonic heart development. Further analysis of Nkx2.5Cre/+ ; Ggppsfl/fl mutants showed that the loss of Ggpps caused disorganized cardiac cytoarchitecture as early as E11.5 by disturbing cell-cell junctions. Ggpps inactivation decreased Rho GTPase geranylgeranylation and their activity, which might account for the disruption of cell-cell junctions. Moreover, elevating the protein geranylgeranylation by supplement of geranylgeranyl pyrophosphate (GGPP) could recover the Ggpps deficient induced defects of cytoarchitecture and cell-cell junctions in vitro and in vivo. Conclusion Our present study demonstrates that GGPPS-mediated protein geranylgeranylation plays an indispensable role in the ventricular chamber maturation and acts as a stage-specific signal to regulate the establishment of cardiac cytoarchitecture during mid-gestation. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
8. GGPP depletion initiates metaflammation through disequilibrating CYB5R3-dependent eicosanoid metabolism.
- Author
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Lisha Wei, Yan-Yan Zheng, Jie Sun, Pei Wang, Tao Tao, Yeqiong Li, Xin Chen, Yongjuan Sang, Danyang Chong, Wei Zhao, Yuwei Zhou, Ye Wang, Zhihui Jiang, Tiantian Qiu, Chao-Jun Li, Min-Sheng Zhu, and Xuena Zhang
- Subjects
- *
METABOLISM , *METABOLIC disorders , *ENDOPLASMIC reticulum , *SMOOTH muscle , *ISOPRENYLATION , *ISOPENTENOIDS - Abstract
Metaflammation is a primary inflammatory complication of metabolic disorders characterized by altered production of many inflammatory cytokines, adipokines, and lipid mediators. Whereas multiple inflammation networks have been identified, the mechanisms by which metaflammation is initiated have long been controversial. As the mevalonate pathway (MVA) produces abundant bioactive isoprenoids and abnormal MVA has a phenotypic association with inflammation/immunity, we speculate that isoprenoids from the MVA may provide a causal link between metaflammation and metabolic disorders. Using a line with the MVA isoprenoid producer geranylgeranyl diphosphate synthase (GGPPS) deleted, we find that geranylgeranyl pyrophosphate (GGPP) depletion causes an apparent metaflammation as evidenced by abnormal accumulation of fatty acids, eicosanoid intermediates, and proinflammatory cytokines. We also find that GGPP prenylate cytochrome b5 reductase 3 (CYB5R3) and the prenylated CYB5R3 then translocate from the mitochondrial to the endoplasmic reticulum (ER) pool. As CYB5R3 is a critical NADH-dependent reductase necessary for eicosanoid metabolism in ER, we thus suggest that GGPP-mediated CYB5R3 prenylation is necessary for metabolism. In addition, we observe that pharmacological inhibition of the MVA pathway by simvastatin is sufficient to inhibit CYB5R3 translocation and induces smooth muscle death. Therefore, we conclude that the dysregulation of MVA intermediates is an essential mechanism for metaflammation initiation, in which the imbalanced production of eicosanoid intermediates in the ER serve as an important pathogenic factor. Moreover, the interplay of MVA and eicosanoid metabolism as we reported here illustrates a model for the coordinating regulation among metabolite pathways. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
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