Hypoxia preconditioning induced HIF-1α promotes glucose metabolism and protects mitochondria in liver I/R injury

Zhang, Zhuang; Guo, Shu; Ji, Zhipeng; Maoyou, Zhuang; Linglan, Yin; Wang, Gangping; Cheng, Jun; Meng, Zhen; Tian, Jessie; Zhang, Peijian; Xu, Kesen

doi:10.1016/j.clinre.2014.12.012

Cited by 18 publications

(24 citation statements)

References 33 publications

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“…Hypoxic-induced HIF-1α protected hepatocellular mitochondrial injury and cell apoptosis through promoting LDHA expression in liver tissue22. In our study, we found that JB could induce B16F10 cell apoptosis though downregulating the mRNA expression of Ldha .…”

Section: Discussionsupporting

confidence: 52%

“…Moreover, GLUTs are over-expressed in almost all cancer types and hence contribute to the increased glucose utilization that is characteristic of the glycolytic phenotype, a key signature of cancer23. Hypoxic-induced HIF-1α protected hepatocellular mitochondrial injury and cell apoptosis through promoting GLUT1 expression in liver tissue22. In our experiments, JB could block the Glut1 expression to induce B16F10 cell apoptosis.…”

Section: Discussionmentioning

confidence: 56%

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Jolkinolide B induces apoptosis and inhibits tumor growth in mouse melanoma B16F10 cells by altering glycolysis

Gao

Yan

Wang

et al. 2016

Sci Rep

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Most cancer cells preferentially rely on glycolysis to produce the energy (adenosine triphosphate, ATP) for growth and proliferation. Emerging evidence demonstrates that the apoptosis in cancer cells could be closely associated with the inhibition of glycolysis. In this study, we have found that jolkinolide B (JB), a bioactive diterpenoid extracted from the root of Euphorbia fischeriana Steud, induced tumor cells apoptosis and decreased the production of ATP and lactic acid in mouse melanoma B16F10 cells. Furthermore, we found that JB downregulated the mRNA expression of glucose transporter genes (Glut1, Glut3 and Glut4) and glycolysis-related kinase genes (Hk2 and Ldha) in B16F10 cells. Moreover, treatment with JB upregulated the mRNA expression of pro-apoptosis genes (Bax), downregulated the mRNA expression of anti-apoptosis genes (Bcl-2, Caspase-3 and Caspase-9), decreased the potential of mitochondrial membrane and increased reactive oxygen species (ROS) levels in B16F10 cells. Finally, intragastric administration of JB suppressed tumor growth and induced tumor apoptosis in mouse xenograft model of murine melanoma B16F10 cells. Taken together, these results suggest that JB could induce apoptosis through the mitochondrial pathway and inhibit tumor growth. The inhibition of glycolysis could play a crucial role in the induction of apoptosis in JB-treated B16F10 cells.

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 56%

Jolkinolide B induces apoptosis and inhibits tumor growth in mouse melanoma B16F10 cells by altering glycolysis

Gao

Yan

Wang

et al. 2016

Sci Rep

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“…Before the extraction of liver grafts, IPC partly alleviates operation‐induced liver injury and reduces the IL‐6 level, thereby inhibiting the generation of multiple inflammatory cytokines ; thus, the survival time of the liver graft is prolonged . Additionally, the 90‐min hypoxic environment before LT notably increases the expression level of HIF‐1α and protects against hepatic IR injury by promoting glucose metabolism . Addition of ulinastatin and simvastatin inhibits the release of inflammatory cytokines and apoptotic genes in a dose‐dependent manner, thus allowing liver grafts to withstand cold IR .…”

Section: Pre‐conditions For Lt To Eliminate Cold Hepatic Ir Injurymentioning

confidence: 99%

Pre‐conditions for eliminating mitochondrial dysfunction and maintaining liver function after hepatic ischaemia reperfusion

Hu¹

2017

J Cellular Molecular Medi

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The liver, the largest organ with multiple synthesis and secretion functions in mammals, consists of hepatocytes and Kupffer, stem, endothelial, stellate and other parenchymal cells. Because of early and extensive contact with the external environment, hepatic ischaemia reperfusion (IR) may result in mitochondrial dysfunction, autophagy and apoptosis of cells and tissues under various pathological conditions. Because the liver requires a high oxygen supply to maintain normal detoxification and synthesis functions, it is extremely susceptible to ischaemia and subsequent reperfusion with blood. Consequently, hepatic IR leads to acute or chronic liver failure and significantly increases the total rate of morbidity and mortality through multiple regulatory mechanisms. An increasing number of studies indicate that mitochondrial structure and function are impaired after hepatic IR, but that the health of liver tissues or liver grafts can be effectively rescued by attenuation of mitochondrial dysfunction. In this review, we mainly focus on the subsequent therapeutic interventions related to the conservation of mitochondrial function involved in mitigating hepatic IR injury and the potential mechanisms of protection. Because mitochondria are abundant in liver tissue, clarification of the regulatory mechanisms between mitochondrial dysfunction and hepatic IR should shed light on clinical therapies for alleviating hepatic IR‐induced injury.

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“…Mitochondria are dynamic organelles that maintain cellular homeostasis and metabolic balance. Increasing evidence suggests that alterations in mitochondrial function contribute to hepatic pathology during I/R injury [7][8][9][10][11][12][13] . Mitochondrial damage results in excessive generation and accumulation of cellular ROS, which induce apoptosis by directly attacking cellular molecules and promoting inflammatory cells infiltration.…”

Section: Introductionmentioning

confidence: 99%

MSCs ameliorate hepatocellular apoptosis mediated by PINK1-dependent mitophagy in liver ischemia/reperfusion injury through AMPKα activation

Zheng

Chen

et al. 2020

Cell Death Dis

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Hepatocyte apoptosis is the main pathophysiological process underlying liver ischemia/reperfusion (I/R) injury. Mitochondrial abnormalities have a vital role in hepatocellular damage. The hepatoprotective effects of mesenchymal stem cells (MSCs) have been previously demonstrated. In this study, we aim to investigate the effect and potential mechanism of MSCs against liver I/R injury. Effects of MSCs were studied in mice liver I/R injury model and in a hypoxia/reoxygenation (H/R) model of L02 hepatocytes. The potential mechanisms of MSCs on these in vivo and in vitro I/R-induced hepatocellular apoptosis models were studies. Accompanied by the improvement of hepatic damage, MSCs exhibited capabilities of controlling mitochondrial quality, shown by reduced mitochondrial reactive oxygen species (mtROS) overproduction, decreased the accumulation of mitochondrial fragmentation, restored ATP generation and upregulated mitophagy. Furthermore, we descripted a potential mechanism of MSCs on upregulating mitophagy and found that the reduced Parkin and PINK1 expression and inactivated AMPKα pathway were observed in the liver tissue in I/R model. These effects were reversed by MSCs treatment. In vitro study showed that MSCconditioned medium (MSC-CM) suppressed hepatocellular apoptosis and inhibited mtROS accumulation in the H/R environment. And these effects of MSC-CM were partially blocked after the cells were transfected with PINK1 siRNA or added with dorsomorphin. Collectively, our findings provide a novel pharmacological mechanism that MSCs exert hepatoprotective effect in liver I/R injury via upregulating PINK1-dependent mitophagy. In addition, this effect might be attributed to the modulation of AMPKα activation.

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Hypoxia preconditioning induced HIF-1α promotes glucose metabolism and protects mitochondria in liver I/R injury

Cited by 18 publications

References 33 publications

Jolkinolide B induces apoptosis and inhibits tumor growth in mouse melanoma B16F10 cells by altering glycolysis

Jolkinolide B induces apoptosis and inhibits tumor growth in mouse melanoma B16F10 cells by altering glycolysis

Pre‐conditions for eliminating mitochondrial dysfunction and maintaining liver function after hepatic ischaemia reperfusion

MSCs ameliorate hepatocellular apoptosis mediated by PINK1-dependent mitophagy in liver ischemia/reperfusion injury through AMPKα activation

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