Variable responses of small and large human hepatocytes to hypoxia and hypoxia/reoxygenation (H-R)

Bhogal, Ricky H.; Weston, Chris J.; Curbishley, Stuart M.; Bhatt, Anand N.; Adams, David H.; Afford, Simon C.

doi:10.1016/j.febslet.2011.02.030

Cited by 14 publications

(13 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hypoxia-induced cell death is a major concern in various clinical settings and plays a critical role in various physiopathological processes, such as hypoxic/ischemic disease, organ transplantation, angiogenesis or tumor invasion ( 33 – 35 ). I/R injury comprises a series of events that may occur together or separately: Reperfusion arrhythmias, myocardial stunning in ‘reversible mechanical dysfunction’, microvascular damage and cell death ( 36 – 38 ).…”

Section: Discussionmentioning

confidence: 99%

Hypoxia induces autophagy in cardiomyocytes via a hypoxia-inducible factor 1-dependent mechanism

Gui

Liu

2016

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Hypoxia frequently accompanies such vascular disorders as atherosclerosis, thrombosis and ischemia/reperfusion injury. Myocardial ischemia/reperfusion, in particular, is a major contributor to cardiomyocyte impairment. Autophagy is a dynamic, self-catabolic process that has been implicated in a wide range of physiological processes and the pathogenesis of diverse diseases. The aim of the present study was to investigate the promotion of autophagy by hypoxia in a rat H9c2 heart cell line and determine the regulatory role of hypoxia-inducible factor 1 (HIF-1) in the hypoxia-induced autophagy in H9c2 cells, using quantitative green fluorescent protein-microtubule-associated protein 1 light chain 3 analysis and electron microscopy of autophagic vesicles. In addition, western blot and quantitative polymerase chain reaction analysis of autophagy-associated markers was conducted. In addition, the role of HIF-1-mediated autophagy in the hypoxia-induced impairment of H9c2 cells was examined, as a measure of cellular viability, using an MTT assay. The results demonstrated that autophagy was induced in H9c2 cells under hypoxia, and the autophagy induction triggered by hypoxia could be enhanced by HIF-1α overexpression and inhibited by HIF-1α knockdown. Furthermore, the HIF-1-mediated autophagy ameliorated the reduction in the H9c2 cell viability induced by hypoxia. These findings provide a novel insight into the hypoxic-ischemic injury to cardiomyocytes and give evidence for the occurrence of HIF-1-mediated autophagy in myocardial ischemia.

show abstract

Section: Discussionmentioning

confidence: 99%

Hypoxia induces autophagy in cardiomyocytes via a hypoxia-inducible factor 1-dependent mechanism

Gui

Liu

2016

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…These changes cause local hypoxia, which may have an effect on PDLCs and cause release of chemical mediators, resulting in adaptive responses to maintain homoeostasis of periodontal tissue. Hypoxia-induced cell death is a major concern in various clinical settings such as hypoxic/ischaemic disease, organ transplantation, and others (21,(30)(31)(32). To elucidate the mechanisms by which human PDLCs respond to hypoxia, we used treating them with CoCl 2 as a model, and demonstrated that CoCl 2 triggered both apoptosis and autophagy in PDLCs involving the HIF-1a pathway.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia induces apoptosis and autophagic cell death in human periodontal ligament cells through HIF‐1α pathway

et al. 2012

View full text Add to dashboard Cite

show abstract

“…16 Here we demonstrate that large/PV hepatocytes ( Fig. 10) increase autophagy significantly more than PP/small human hepatocytes during H-R (Fig.…”

Section: Resultsmentioning

confidence: 90%

Autophagy

et al. 2012

Self Cite

View full text Add to dashboard Cite

The role of autophagy in the response of human hepatocytes to oxidative stress remains unknown. Understanding this process may have important implications for the understanding of basic liver epithelial cell biology and the responses of hepatocytes during liver disease. To address this we isolated primary hepatocytes from human liver tissue and exposed them ex vivo to hypoxia and hypoxia-reoxygenation (H-R). We showed that oxidative stress increased hepatocyte autophagy in a reactive oxygen species (ROS) and class III PtdIns3K-dependent manner. Specifically, mitochondrial ROS and NADPH oxidase were found to be key regulators of autophagy. Autophagy involved the upregulation of BECN1, LC3A, Atg7, Atg5 and Atg 12 during hypoxia and H-R. Autophagy was seen to occur within the mitochondria of the hepatocyte and inhibition of autophagy resulted in the lowering a mitochondrial membrane potential and onset of cell death. Autophagic responses were primarily observed in the large peri-venular (PV) hepatocyte subpopulation. Inhibition of autophagy, using 3-methyladenine, increased apoptosis during H-R. Specifically, PV human hepatocytes were more susceptible to apoptosis after inhibition of autophagy. These findings show for the first time that during oxidative stress autophagy serves as a cell survival mechanism for primary human hepatocytes.

show abstract

Variable responses of small and large human hepatocytes to hypoxia and hypoxia/reoxygenation (H-R)

Cited by 14 publications

References 20 publications

Hypoxia induces autophagy in cardiomyocytes via a hypoxia-inducible factor 1-dependent mechanism

Hypoxia induces autophagy in cardiomyocytes via a hypoxia-inducible factor 1-dependent mechanism

Hypoxia induces apoptosis and autophagic cell death in human periodontal ligament cells through HIF‐1α pathway

Autophagy

Contact Info

Product

Resources

About