Alpha-lipoic acid protects against pressure overload-induced heart failure via ALDH2-dependent Nrf1-FUNDC1 signaling

Li, Wenjia; Yin, Lei; Sun, Xiaolei; Wu, Jian; Dong, Zhen; Hu, Kai; Sun, Aijun; Ge, Junbo

doi:10.1038/s41419-020-02805-2

Cited by 48 publications

(39 citation statements)

References 47 publications

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“…[109], FGF12 [110], AQP4 [111], LMOD2 [112], SELENBP1 [113], MB (myoglobin) [114], S100A1 [115], RYR2 [116], GPC5 [117], JARID2 [118], EGFR (epidermal growth factor receptor) [119], FUNDC1 [120], S1PR1 [121], EPAS1 [122] and OSBPL11 [123] genes are a potential biomarkers for the detection and prognosis of HF at an early age. A previous study reported that CALR (calreticulin) [124], BSCL2 [125], PKD1 [126], TMBIM1 [127], CHST15 [128], NAA10 [129], TCF3 [130], CNN1 [131], TAF1A [132], ACAD9 [133], KLHL24 [134], MYOM2 [135], TRIM63 [136] [210] are the key biomarkers in cardiac hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

Identification of biomarkers, pathways and potential therapeutic targets for heart failure using bioinformatics analysis

Vastrad¹,

Vastrad²

2021

Preprint

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Heart failure (HF) is a complex cardiovascular diseases associated with high mortality. To discover key molecular changes in HF, we analyzed next-generation sequencing (NGS) data of HF. In this investigation, differentially expressed genes (DEGs) were analyzed using limma in R package from GSE161472 of the Gene Expression Omnibus (GEO). Then, gene enrichment analysis, protein-protein interaction (PPI) network, miRNA-hub gene regulatory network and TF-hub gene regulatory network construction, and topological analysis were performed on the DEGs by the Gene Ontology (GO), REACTOME pathway, STRING, HiPPIE, miRNet, NetworkAnalyst and Cytoscape. Finally, we performed receiver operating characteristic curve (ROC) analysis of hub genes. A total of 930 DEGs 9464 up regulated genes and 466 down regulated genes) were identified in HF. GO and REACTOME pathway enrichment results showed that DEGs mainly enriched in localization, small molecule metabolic process, SARS-CoV infections and the citric acid (TCA) cycle and respiratory electron transport. Subsequently, the PPI network, miRNA-hub gene regulatory network and TF-hub gene regulatory network were constructed, and 10 hub genes in these network were focused on by centrality analysis and module analysis. Furthermore, data showed that HSP90AA1, ARRB2, MYH9, HSP90AB1, FLNA, EGFR, PIK3R1, CUL4A, YEATS4 and KAT2B were good diagnostic values. In summary, this study suggests that HSP90AA1, ARRB2, MYH9, HSP90AB1, FLNA, EGFR, PIK3R1, CUL4A, YEATS4 and KAT2B may act as the key genes in HF.

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Section: Discussionmentioning

confidence: 99%

Identification of biomarkers, pathways and potential therapeutic targets for heart failure using bioinformatics analysis

Vastrad¹,

Vastrad²

2021

Preprint

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“…The FUNDC1 is a highly conserved mitochondrial outer membrane protein. Similar to BNIP3/NIX, it directly interacts with LC3 through the N end, mediating hypoxia-induced mitophagy, which is widely expressed in various cells, tissues, and organs, particularly heart ( 63 , 79 , 88 , 90 , 92 , 93 ). Under normal oxygen conditions, FUNDC1 phosphorylated by semi refined carrageenan (SRC) kinases and Casein kinase II (CK2) decreases their affinity to LC3, which effectively inhibits mitophagy.…”

Section: The Physiological State Of Mitochondrial Dynamics and Mitophagymentioning

confidence: 99%

“…During hypoxia, it is FUNDC1 dephosphorylated by 13 phosphatases (such as PGAM5) of serine, triggering its binding to LC3 and improving mitophagy activity. It removes damaged mitochondria ( 23 , 79 , 88 , 92 , 93 , 142 – 144 ). Hypoxia can activate poly (ADP-ribose) polymerase (PARP), promoting mitophagy by regulating mitochondrial membrane potential and inducing cardiomyocyte apoptosis, ROS is central for PARP mediated mitochondrial membrane potential (ΔΨm) decline, and inhibited PARP can reduce the production after injury ( 80 ).…”

Section: The Pathophysiological State Of Mitochondrial Dynamics and Mitophagymentioning

confidence: 99%

“…Moreover, protein kinase A activity is significantly inhibited at low glucose levels, enhancing the positioning capacity of DRP1 on the outer membrane of the mitochondria, which significantly increases the rate of mitochondrial fission ( 183 ). Past studies have established that hunger or reduced insulin signals are a strong trigger for autophagy ( 92 , 184 , 185 ). Hyperglycemia can induce myocardial mitochondria division but inhibit mitophagy, causing the accumulation of functionally impaired mitochondria ( 57 , 186 , 187 ).…”

Section: The Pathophysiological State Of Mitochondrial Dynamics and Mitophagymentioning

confidence: 99%

See 1 more Smart Citation

Advances in Cardiotoxicity Induced by Altered Mitochondrial Dynamics and Mitophagy

Yin

Shen

2021

Front. Cardiovasc. Med.

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Mitochondria are the most abundant organelles in cardiac cells, and are essential to maintain the normal cardiac function, which requires mitochondrial dynamics and mitophagy to ensure the stability of mitochondrial quantity and quality. When mitochondria are affected by continuous injury factors, the balance between mitochondrial dynamics and mitophagy is broken. Aging and damaged mitochondria cannot be completely removed in cardiac cells, resulting in energy supply disorder and accumulation of toxic substances in cardiac cells, resulting in cardiac damage and cardiotoxicity. This paper summarizes the specific underlying mechanisms by which various adverse factors interfere with mitochondrial dynamics and mitophagy to produce cardiotoxicity and emphasizes the crucial role of oxidative stress in mitophagy. This review aims to provide fresh ideas for the prevention and treatment of cardiotoxicity induced by altered mitochondrial dynamics and mitophagy.

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“…It has been used as one of the dietary supplements to prevent and treat many diseases, including stroke, diabetes, neurodegenerative and hepatic disorders [13]. In experimental studies, ALA has shown bene cial effects against cardiovascular dysfunction [17], sepsis [18], endothelin dysfunction and oxidative stress [19], testicular dysfunction [20] and liver dysfunction [21]. Recently, ALA has been clinically tested for its bene cial effects in patients with bromyalgia pain [14], multiple sclerosis [22], obesity [23], β-thalassemia [24], diabetes [25], non-alcoholic fatty liver disease [26].…”

Section: Introductionmentioning

confidence: 99%

α-Lipoic Acid Induces Intrinsic Apoptosis in Human Oral Squamous Carcinoma Cells

Duraisamy

Ezhilarasan

Elangovan

2021

Preprint

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Oral squamous cell carcinoma is one of the leading cancers in India and it is responsible for significant morbidity and mortality. α -lipoic acid, a co-factor for several metabolic enzymes, suppresses the tumor growth. In this study, we investigated the α-lipoic acid-induced cytotoxicity and apoptosis in human oral squamous carcinoma (SCC-25) cells. α-lipoic acid treatments were given to SCC-25 cells for 24 h and cell proliferation was evaluated by MTT assay. The reactive oxygen species expression was examined by dichloro-dihydro-fluorescein diacetate assay. Apoptosis-related morphological changes were detected by dual staining. Cytochrome c and RAS (H-Ras) expression was measured by dual staining and RT-PCR respectively. Intrinsic apoptosis-related markers are analyzed using qPCR.α-lipoic acid inhibited SCC-25 cell proliferation in a concentration-dependent manner. This treatment also increased intracellular reactive oxygen species expression and the percentage of apoptotic cells (up to 70% of the cell population). Dual staining further confirms cytochrome c cytosolic expression. The oncogene H-Ras protein and gene expression was also down-regulated upon α-lipoic acid treatment in SCC-25 cells. qPCR analysis further confirms α-lipoic acid-induced an upregulation of bax, Apaf-1, caspase 3 and − 9, pro-apoptotic gene expressions and downregulation of bcl-2, an anti-apoptotic gene expression. The present results suggest that α-lipoic acid has cytotoxic and pro-apoptotic potential and it also downregulates H-Ras oncogene expression in human oral squamous carcinoma cells. α-lipoic acid may have promising role in the treatment of human oral squamous carcinoma.

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Alpha-lipoic acid protects against pressure overload-induced heart failure via ALDH2-dependent Nrf1-FUNDC1 signaling

Cited by 48 publications

References 47 publications

Identification of biomarkers, pathways and potential therapeutic targets for heart failure using bioinformatics analysis

Identification of biomarkers, pathways and potential therapeutic targets for heart failure using bioinformatics analysis

Advances in Cardiotoxicity Induced by Altered Mitochondrial Dynamics and Mitophagy

α-Lipoic Acid Induces Intrinsic Apoptosis in Human Oral Squamous Carcinoma Cells

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