Sevoflurane preconditioning attenuates hypoxia/reoxygenation injury of H9c2 cardiomyocytes by activation of the HIF-1/PDK-1 pathway

Hou, Tianliang; Ma, Haiping; Wang, Haixia; Chen, Chunling; Ye, Jianrong; Ahmed, Ahmed Mohamed; Zheng, Hong

doi:10.7717/peerj.10603

Cited by 11 publications

(10 citation statements)

References 34 publications

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“…For the establishment of SI-AKI cell model, HK-2 cells were stimulated with 10 μg/mL LPS (Sigma) for 24 h. 23 For SEV treatment, cells were pre-treated with 2.4% SEV (Sigma) for 1 h. 9,24 To inhibit SIRT1, LPS plus SEV-treated HK-2 cell line was co-treated with 10 μM EX527 (MedChem Express), an inhibitor of SIRT1, for 24 h. 25…”

Section: Introductionmentioning

confidence: 99%

Sevoflurane ameliorates LPS-induced inflammatory injury of HK-2 cells through Sirtuin1/NF-κB pathway

Wang

Yin

et al. 2022

Allergol Immunopathol

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The anesthetic sevoflurane (SEV) has been shown to protect against organ’s injury during sepsis. The present study intended to uncover the protective effects of SEV on sepsis-induced acute kidney injury (SI-AKI) and its possible mechanism. Human renal tubular epithelial cell HK-2 was treated with 10 μg/mL lipopolysaccharide (LPS) to construct SI-AKI cell model. LPS-induced HK-2 cells were pretreated with SEV in the absence or presence of EX527, an inhibitor of Sirtuin 1 (SIRT1), after which were the detection of cell viability, lactate dehydrogenase (LDH) release, apoptosis, inflammation, and oxidative stress. Our results demonstrated that LPS caused decreased cell viability, increased LDH release, improved cell apoptosis along with decreased expression of Bcl2 and enhanced expressions of Bax, cleaved PARP and cleaved caspase, enhanced production, and protein expressions of TNF-α, IL-6, and IL-1β, increased generation of reactive oxygen species (ROS) and malondialdehyde (MDA), but contributed to declined activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). LPS inhibited SIRT1 and IκBα expressions but upregulated p-NF-κB p65 and acetyl-p53 expressions as well. However, SEV pretreatment abolished all above-mentioned effects of LPS on HK-2 cells, while EX527 significantly reversed the effects of SEV. In conclusion, SEV effectively protected HK-2 cells against LPS-induced apoptosis, inflammation, and oxidative stress, and these effects may depend on the increase of SIRT1 expression, thereby inactivating NF-κB signaling.

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Section: Introductionmentioning

confidence: 99%

Sevoflurane ameliorates LPS-induced inflammatory injury of HK-2 cells through Sirtuin1/NF-κB pathway

Wang

Yin

et al. 2022

Allergol Immunopathol

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“…We speculate that this is because HNK reduces the expression of HIF-1α protein, which in turn inhibits the transcription of key molecules GLUT1, HK2, and PDK1 on the glycolysis link, resulting in a decrease in the glycolysis level of cancer cells. Moreover, these interventions of HNK on glycolysis ultimately indirectly inhibited the proliferation of breast cancer cells and slowed the growth of tumors ( Hou et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Honokiol Inhibits HIF-1α-Mediated Glycolysis to Halt Breast Cancer Growth

Huang

et al. 2022

Front. Pharmacol.

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Background: Hypoxia-inducible factor-1α (HIF-1α) induces the expression of glycolysis-related genes, which plays a direct and key role in Warburg effect. In a recent study, honokiol (HNK) was identified as one of the potential agents that inhibited the HIF-1α signaling pathway. Because the HIF- 1α pathway is closely associated with glycolysis, we investigated whether HNK inhibited HIF-1α-mediated glycolysis.Methods: The effects of HNK on HIF-1α-mediated glycolysis and other glycolysis-related genes’ expressions, cancer cells apoptosis and tumor growth were studied in various human breast cancer models in vitro and in vivo. We performed the following tests: extracellular acidification and oxygen consumption rate assays, glucose uptake, lactate, and ATP assays for testing glycolysis; WST-1 assay for investigating cell viability; colony formation assay for determining clonogenicity; flow cytometry for assessing cell apoptosis; qPCR and Western blot for determining the expression of HIF-1α, GLUT1, HK2 and PDK1. The mechanisms of which HNK functions as a direct inhibitor of HIF-1α were verified through the ubiquitination assay, the Co-IP assay, and the cycloheximide (CHX) pulse-chase assay.Results: HNK increased the oxygen consumption rate while decreased the extracellular acidification rate in breast cancer cells; it further reduced glucose uptake, lactic acid production and ATP production in cancer cells. The inhibitory effect of HNK on glycolysis is HIF-1α-dependent. HNK also downregulated the expression of HIF-1α and its downstream regulators, including GLUT1, HK2 and PDK1. A mechanistic study demonstrated that HNK enhanced the self-ubiquitination of HIF-1α by recruiting two E3 ubiquitin ligases (UFL1 and BRE1B). In vitro, HNK inhibited cell proliferation and clonogenicity, as well as induced apoptosis of cancer cells. These effects were also HIF1α-dependent. In vivo, HNK inhibited tumor growth and HIF-1α-mediated glycolysis.Conclusion: HNK has an inhibitory effect on HIF-1α-mediated glycolysis in human breast cancer. Our research revealed a new mechanism of HNK as an anti-cancer drug, thus representing a novel strategy to improve the prognosis of cancer.

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“…Approximately 90-95% of ATP production comes from oxidative phosphorylation of mitochondria, and glycolysis accounts for the rest. Mitochondrial fatty acid oxidation is the main source of ATP in many tissues and organs (34). Fatty acid oxidation is a complex biological process involving mitochondrial β-oxidation, TCA cycle activity, and the ETC (35).…”

Section: K Lmentioning

confidence: 99%

“…Alterations in fatty acid metabolism can contribute to a variety of pathologies and cell dysfunction (36). Mitochondrial fatty acid oxidation is the main source of ATP in many tissues and organs (34,37). The maintenance of lipid homeostasis is a highly complex process involving lipid storage, synthesis, and utilization.…”

Section: K Lmentioning

confidence: 99%

High-fat diet-induced obesity primes fatty acid β-oxidation impairment and consequent ovarian dysfunction during early pregnancy

Li¹,

Guo²,

Yang³

et al. 2021

Ann Transl Med

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Background: Obesity is associated with many adverse effects on female fertility. Obese women have a higher likelihood of developing ovulatory dysfunction due to dysregulation of the hypothalamic-pituitaryovarian axis. However, the effect of obesity on ovarian function during early pregnancy needs to be further assessed.Methods: C57BL6/J mice were given a high-fat diet (HFD) for 12 weeks to induce obesity. An in vitro high-fat model was established by treating the human ovarian granulosa cell line KGN with oleic acid and palmitic acid. Ovarian morphology of obese mice in early pregnancy was assessed by hematoxylin and eosin staining and ovarian function was assessed by enzyme-linked immunosorbent assay, western blotting, and immunohistochemistry. Oil Red O staining and transmission electron microscopy were used to detect fatty acid accumulation. Specific markers relating to the ovarian functional mechanism were assessed by real-time PCR, western blotting, lactate detection, adenosine triphosphate (ATP) detection, biochemical analyses, and enzyme-linked immunosorbent assay. Results:The results of this study showed that during early pregnancy, the number of corpus lutea, serum estradiol and progesterone levels, and the expression of the steroid biosynthesis-related protein CYP19A1 (aromatase), CYP11A1 (cholesterol side chain cleavage enzyme), and StAR (steroidogenic acute regulatory protein), were significantly increased in HFD mice. Mice fed an HFD also showed a significant increase in ovarian lipid accumulation on day 7 of pregnancy. Genes involved in fatty acid synthesis (Acsl4 and Elovl5), and fatty acid uptake and transport (Slc27a4), together with the β-oxidation rate-limiting enzyme Cpt1a, were significantly upregulated in HFD mice. Specifically, there was abnormal elevation of ATP and aberrant expression of tricarboxylic acid cycle (TCA)-and electron transport chain (ETC)-related genes in the ovaries of pregnant HFD mice. KGN cells treated with etomoxir targeting β-oxidation of fatty acid showed decreased TCA cycle and ETC related gene expression. The elevation of ATP and estradiol and progesterone levels was reversed.Conclusions: During early pregnancy, HFD-induced obesity increases fatty acid β-oxidation, which in turn increases TCA cycle and ETC related gene expression, leading to increased ATP production and ovarian dysfunction.

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Sevoflurane preconditioning attenuates hypoxia/reoxygenation injury of H9c2 cardiomyocytes by activation of the HIF-1/PDK-1 pathway

Cited by 11 publications

References 34 publications

Sevoflurane ameliorates LPS-induced inflammatory injury of HK-2 cells through Sirtuin1/NF-κB pathway

Sevoflurane ameliorates LPS-induced inflammatory injury of HK-2 cells through Sirtuin1/NF-κB pathway

Honokiol Inhibits HIF-1α-Mediated Glycolysis to Halt Breast Cancer Growth

High-fat diet-induced obesity primes fatty acid β-oxidation impairment and consequent ovarian dysfunction during early pregnancy

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