Proline improves cardiac remodeling following myocardial infarction and attenuates cardiomyocyte apoptosis via redox regulation

Wang, Jiacheng; Xue, Zhenyi; Lin, Jun; Wang, Yao; Ying, Hangying; Lv, Qingyu; Hua, Chunting; Wang, Meihui; Chen, Siji; Zhou, Bin-quan

doi:10.1016/j.bcp.2020.114065

Cited by 41 publications

(37 citation statements)

References 47 publications

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“…Apoptosis was detected with an Annexin V-FITC/PI Apoptosis Detection Kit (KGA108, KeyGen, China) and TUNEL using an In Situ Cell Death Detection Kit (Roche, USA) according to the manufacturer's instructions as we described previously [ 11 ].…”

Section: Methodsmentioning

confidence: 99%

“…ROS levels in H9c2 cells were measured by flow cytometry with the fluorescent probe DCFH-DA (10 μ M) (Sigma, USA, D6883) as we described previously [ 11 ]. The fluorescence probe DHE was used to measure intracellular superoxide anion levels.…”

Section: Methodsmentioning

confidence: 99%

“…A detailed methodology can be found in our previous description [ 11 ]. The sequences of the primers were as follows: β -actin (forward, 5′-AAGTCCCTCACCCTCCCAAAAG-3′, reverse, 5′-AAGCAATGCTGTCACCTTCCC-3′) and PRODH (forward, 5′-GCCAGTGACGGTGGTTTTTC-3′, reverse, 5′-CATCTTGGCGATGCTCTCCT-3′).…”

Section: Methodsmentioning

confidence: 99%

“…A detailed methodology can be found in our previous description [ 11 ]. Primary antibodies against the following proteins were used in the present study: β -actin (#100118, GeneTex), PRODH (#22980-1-AP, Proteintech), and cleaved caspase 3 (#19677-1-AP, Proteintech).…”

Section: Methodsmentioning

confidence: 99%

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Metabolomic Analysis of the Ameliorative Effect of Enhanced Proline Metabolism on Hypoxia-Induced Injury in Cardiomyocytes

Wang

Xue

Hua

et al. 2020

Oxidative Medicine and Cellular Longevity

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Background. Coronary heart disease is currently the leading cause of death in humans. Its poor prognosis and high mortality are associated with myocardial ischemia, which leads to metabolic disorder-related cardiomyocyte apoptosis and reactive oxygen species (ROS) production. Previous cardiovascular metabolomics studies in humans and mice have shown that proline metabolism is severely altered after cardiomyocyte hypoxia. Proline dehydrogenase (PRODH) is located on the inner mitochondrial membrane and is an enzyme that catalyzes the first step of proline catabolism, which plays an important role in improving the cellular redox state. In vitro oxygen-glucose deprivation can mimic in vivo myocardial ischemic injury. This study is aimed at investigating whether enhancing proline metabolism by overexpressing PRODH can ameliorate hypoxia-induced injury in cardiomyocytes and to reveal the related altered metabolites and mechanistic pathway via untargeted metabolomics analysis. Methods and Results. First, through public database analysis and RT-qPCR and western blot analyses in a cardiomyocyte hypoxia model, we found that the expression of the proline-degrading enzyme PRODH was downregulated after myocardial infarction and hypoxia exposure. Second, LDH assays, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), DHE staining, flow cytometric apoptosis analysis with DCFH and Annexin V-FITC/PI, and western blot analysis were used to assess the injury level in cardiomyocytes. Enhanced proline metabolism induced by PRODH overexpression reduced the levels of reactive oxidative stress and apoptosis, whereas PRODH knockdown had the opposite effects. Third, untargeted metabolomics analysis revealed that the protective effect was associated with significant changes in metabolism linked to sphingolipid signaling pathways, unsaturated fatty acid biosynthesis, phosphocreatine, glutathione disulfide, aminoacyl-tRNA biosynthesis, and ABC transporters. Conclusions. Our study demonstrated a protective effect of enhanced proline metabolism in cardiomyocytes under hypoxia, providing a novel strategy for exploring new treatments for coronary heart disease.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Metabolomic Analysis of the Ameliorative Effect of Enhanced Proline Metabolism on Hypoxia-Induced Injury in Cardiomyocytes

Wang

Xue

Hua

et al. 2020

Oxidative Medicine and Cellular Longevity

Self Cite

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“…The transcriptome data were ltered and analyzed according to published paper with minor modi cation [17]. Differential expression analysis and the signi cant levels of GO terms were all performed with Q value ≤ 0.05.…”

Section: De Novo Assembly and Functional Annotation Of Sequencingmentioning

confidence: 99%

Characterization of Genes Associated with TGA7 During the Floral Transition

Chen

et al. 2020

Preprint

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BackgroundThe TGA family has ten members and plays vital roles in plant defence and development in Arabidopsis. However, involvement of TGAs in control of flowering time remains largely unknown and requires further investigation. ResultsTo study the role of TGA7 during the floral transition, we first tested phenotypes of tga7 mutant, which displayed delay-flowering phenotype under both long-day and short-day conditions. We then performed flowering genetic pathways analysis and found that both autonomous and thermosensory pathways may affect TGA7 expression. Furthermore, to reveal differential gene expression profiles between wild-type (WT) and tga7, cDNA libraries were generated for WT and tga7 mutant seedlings at 9 DAG (days after germination). For each library, deep-sequencing produced approximately 6.67 Gb of high-quality sequences with the majority (84.55%) of mRNAs between 500 and 3000 nucleotides in length. Three hundred and twenty-five differentially expressed genes (DEGs) were identified between WT and tga7 mutant seedlings. Among them, four genes are associated with flowering time control. Differential expression of the four flowering-related DEGs was further validated by qRT-PCR.ConclusionsTransciptomic sequencing coupled with flowering genetic pathways analysis provides a framework for further studying the role of TGA7 in promoting flowering.

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Astaxanthin ameliorated isoproterenol induced myocardial infarction via improving the mitochondrial function and antioxidant activity in rats

Mahmoud,

Kamel,

El‐Sayed

et al. 2024

J Biochem & Molecular Tox

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The present study evaluated the cardioprotective effect of astaxanthin (ASX) against isoproterenol (ISO) induced myocardial infarction in rats via the pathway of mitochondrial biogenesis as the possible molecular target of astaxanthin. The control group was injected with normal physiological saline subcutaneously for 2 days. The second group was injected with ISO at a dose of 85 mg/kg bwt subcutaneously for 2 days. The third, fourth and fifth groups were supplemented with ASX at doses of 10, 20, 30 mg/kg bwt, respectively daily by oral gavage for 21 days then injected with ISO dose of 85 mg/kg bwt subcutaneously for 2 successive days. Isoproterenol administration in rats elevated the activities of Creatine kinase‐MB (CK‐MB), aspartate transaminase (AST), lactate dehydrogenase (LDH), and other serum cardiac biomarkers Troponin‐I activities, oxidative stress biomarkers, malondialdehyde(MDA), Nuclear factor‐kappa B (NF‐KB), while it decreased Peroxisome proliferator‐activated receptor‐gamma coactivator (PGC‐1α), Nuclear factor erythroid‐2‐related factor 2 (Nfe212), mitochondrial transcriptional factor A (mt TFA), mitochondrial DNA copy number and glutathione system parameters. However, Astaxanthin decreased the activities of serum AST, LDH, CK‐MB, and Troponin I that elevated by ISO. In addition, it increased glutathione peroxidase and reductase activities, total glutathione and reduced GSH content, and GSH/GSSG ratio, mtDNA copy number, PGC‐1α expression and Tfam expression that improved mitochondrial biogenesis while it decreased GSSG and MDA contents and NF‐KB level in the cardiac tissues. This study indicated that astaxanthin relieved isoproterenol induced myocardial infarction via scavenging free radicals and reducing oxidative damage and apoptosis in cardiac tissue.

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Proline improves cardiac remodeling following myocardial infarction and attenuates cardiomyocyte apoptosis via redox regulation

Cited by 41 publications

References 47 publications

Metabolomic Analysis of the Ameliorative Effect of Enhanced Proline Metabolism on Hypoxia-Induced Injury in Cardiomyocytes

Metabolomic Analysis of the Ameliorative Effect of Enhanced Proline Metabolism on Hypoxia-Induced Injury in Cardiomyocytes

Characterization of Genes Associated with TGA7 During the Floral Transition

Astaxanthin ameliorated isoproterenol induced myocardial infarction via improving the mitochondrial function and antioxidant activity in rats

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