Alpha-lipoic acid activates eNOS through activation of PI3-kinase/Akt signaling pathway

Zhao, Ying; Xie, Xiaoyun; Chen, Minjie; Yi, Kevin; Rajagopalan, Sanjay

doi:10.1016/j.vph.2014.11.004

Cited by 23 publications

(15 citation statements)

References 29 publications

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“…As shown in Figure 5, eight target genes of 16 miRNAs are involved in the PI3K pathway across seven cancer types, based on KEGG (Release 79.1, http://www.genome.jp/kegg/) and studies from Waugh MG [58], Ying Z et al . [59], and Yun YR et al . [60].…”

Section: Resultsmentioning

confidence: 99%

Identification of key differentially expressed MicroRNAs in cancer patients through pan-cancer analysis

Dingerdissen

Gupta

et al. 2018

Computers in Biology and Medicine

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microRNAs (miRNAs) functioning in gene silencing have been associated with cancer progression. However, common abnormal miRNA expression patterns and their potential roles in cancer have not yet been evaluated. To account for individual differences between patients, we retrieved miRNA sequencing data for 575 patients with both tumor and adjacent nontumorous tissues from 14 cancer types from The Cancer Genome Atlas (TCGA). We then performed differential expression analysis using DESeq2 and edgeR. Results showed that cancer types can be grouped based on the distribution of miRNAs with different expression patterns between tumor and non-tumor samples. We found 81 significantly differentially expressed miRNAs (SDEmiRNAs) in a single cancer. We also found 21 key SDEmiRNAs (nine over-expressed and 12 under-expressed) associated with at least eight cancers each and enriched in more than 60% of patients per cancer, including four newly identified SDEmiRNAs (hsa-mir-4746, hsa-mir-3648, hsa-mir-3687, and hsa-mir-1269a). The downstream effects of these 21 SDEmiRNAs on cellular function were evaluated through enrichment and pathway analysis of 7,186 protein-coding gene targets mined from literature reports of differential expression of miRNAs in cancer. This analysis enables identification of SDEmiRNA functional similarity in cell proliferation control across a wide range of cancers, and assembly of common regulatory networks over cancer-related pathways. These findings were validated by construction of a regulatory network in the PI3K pathway. This study provides evidence for the value of further analysis of SDEmiRNAs as potential biomarkers and therapeutic targets for cancer diagnosis and treatment.

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Section: Resultsmentioning

confidence: 99%

Identification of key differentially expressed MicroRNAs in cancer patients through pan-cancer analysis

Dingerdissen

Gupta

et al. 2018

Computers in Biology and Medicine

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“…It has previously been observed that LA activates eNOS by activating Akt signaling (34). By contrast, inhibition of Akt signaling by high levels of UA may be associated with UA-induced insulin resistance, indicating that Akt signaling serves an essential role in endothelial cell function (35).…”

Section: Discussionmentioning

confidence: 99%

Protective role of α-lipoic acid in hyperuricemia-induced endothelial dysfunction

Zou

Wang

Liu

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. The aim of the current study was to determine the effects of α-lipoic acid (LA) on hyperuricemia and endothelial dysfunction, and to uncover the underlying mechanism of its action. A hyperuricemic rat model was established by administration of uric acid (UA) and the rats were orally fed with 2 g/kg/day LA or phosphate-buffered saline. Primary rat aortic endothelial cells were subsequently isolated, and a cell viability assay, apoptosis assay, enzyme nitric oxide synthase (eNOS) activity assay and mitochondrial function assay were all performed. For the in vitro study, human umbilical vein endothelial cells were used and western blotting was performed to assess Akt signaling activity. The results of the current study indicated that LA inhibited apoptosis, enhanced eNOS activity and production of nitric oxide (NO), and rescued mitochondrial mass and function in uric acid (UA)-treated endothelial cells. LA activated Akt signaling and inhibition of Akt signaling abolished the effects of LA on cell viability, NO production, ROS production and ATP levels in UA-treated endothelial cells. Therefore, the current study demonstrated that LA attenuated oxidant stress and inhibited apoptosis in UA-treated endothelial cells by activating Akt signaling. The results indicate that LA may serve as a therapeutic approach to treat hyperuricemia-induced endothelial dysfunction.

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“…PTEN, an important tumor suppressor, is a negative regulator of the PI3K pathway [50]. As shown in Figure 5 [52], and Yun YR et al [53]. miRNAs involved in regulating FGFR family members were also shown in Figure 5, adding another potentially important miRNA, hsa-mir-381, to the pathway.…”

Section: Construction Of Regulatory Network Of Sdemirnas and Their Tmentioning

confidence: 93%

Identification of Key Differentially Expressed MicroRNAs in Cancer Patients Through Pan-cancer Analysis

Dingerdissen

Gupta

et al. 2018

Preprint

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A number of microRNAs (miRNAs) functioning in gene silencing have been associated with cancer progression. However, common expression patterns of abnormally expressed miRNAs and their potential roles in multiple cancer types have not yet been evaluated. To minimize the difference of patients, we collected miRNA sequencing data of 575 patients with tumor and adjacent non-tumorous tissues from 14 cancer types from The Cancer Genome Atlas (TCGA), and performed differential expression analysis using DESeq2 and edgeR. The results showed that cancer types can be grouped based on the distribution of miRNAs with different expression patterns. We found 81 significantly differentially expressed miRNAs (SDEmiRNAs) unique to one of the 14 cancers may affect patient survival rate, and 21 key SDEmiRNAs (nine overexpressed and 12 under-expressed) associated with at least eight cancers and enriched in more than 60% of patients per cancer, including four newly identified SDEmiRNAs (hsa-mir-4746, hsa-mir-3648, hsa-mir-3687, and hsa-mir-1269a). The downstream effect of these 21SDEmiRNAs on cellular functions was evaluated through enrichment and pathway analysis of 7,186 protein-coding gene targets from literature mining with known differential expression profiles in cancers. It enables identification of their functional similarity in cell proliferation control across a wide range of cancers and to build common regulatory networks over cancer-related pathways. This is validated by construction of a regulatory network in PI3K pathway. This study provides evidence of the value of further analysis on SDEmiRNAs as potential biomarkers and therapeutic targets for cancer diagnosis and treatment.

show abstract

Alpha-lipoic acid activates eNOS through activation of PI3-kinase/Akt signaling pathway

Cited by 23 publications

References 29 publications

Identification of key differentially expressed MicroRNAs in cancer patients through pan-cancer analysis

Identification of key differentially expressed MicroRNAs in cancer patients through pan-cancer analysis

Protective role of α-lipoic acid in hyperuricemia-induced endothelial dysfunction

Identification of Key Differentially Expressed MicroRNAs in Cancer Patients Through Pan-cancer Analysis

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