Local interaction of apoptotic hepatocytes and Kupffer cells in a rat model of systemic endotoxemia

Eipel, Christian; Hirschmann, Martin; Abshagen, Kerstin; Menger, Michael D.; Vollmar, Brigitte

doi:10.1111/j.1872-034x.2007.00133.x

Cited by 14 publications

(19 citation statements)

References 32 publications

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“…Haplotype analyses confirmed the dominance of the A (-413)T SNP over (GT)n polymorphism [16] . The results of transient transfection assays using luciferase promoter constructs were consistent with in vitro assays carried out in lymphoblastoid cell lines containing HO-1 GT repeats of various lengths [9] . Cells homozygous for short GT-stretches had significantly greater HO-1 expression and resistance to oxidant-induced apoptosis compared with cells homozygous for long GT-stretches, demonstrating that polymorphisms in GT-stretch length are functionally significant [9] .…”

Section: Polymorphismssupporting

confidence: 79%

“…The reported number of GT-repeats range from 12 to 40, although a bimodal distribution exists in most populations, with the main alleles being composed of 23 or 30 repeats. HO-1 mRNA expression and enzyme expression are greater when GT-repeat lengths are short and lesser when they are long [9] . There is some evidence that links H2O2 or other HO-1 transcriptional activators and the number of GT repetitions and it has been postulated that conformational changes account for the modulation of transcriptional activity.…”

Section: Polymorphismsmentioning

confidence: 95%

“…Control of HO-1 transcription is complex and tightly regulated, with differences in expression found between tissues, as well as between species [9] . A wide variety of stimuli have been shown to induce HO-1 expression, including heme, heavy metals, hydrogen peroxide, oxidized low density lipoproteins, hyperoxia, hypoxia, endotoxins, nitric oxide (and nitric oxide donors), cytokines, angiotensin Ⅱ, shear stress and ultraviolet radiation [3] ( Figure 2).…”

Section: Regulation Of Ho-1mentioning

confidence: 99%

“…The short guanosine/thymine (GT)n [12] repeat in the HO-1 gene promoter may provide protective effects against carotid atherosclerosis in individuals with a high level of arsenic exposure. Therefore, the translation of HO-1 research from "bench to bedside" must be carried out carefully, with the appreciation that the response of HO-1 gene expression to certain stimuli may be different in humans and rodent models [9] . HEME OXYGENASE-1 PROMOTER…”

Section: Regulation Of Ho-1mentioning

confidence: 99%

“…In humans, HO-1 deficiency is associated with susceptibility to oxidative stress and an increased pro-inflammatory state correlated with severe endothelial damage [8] . Mice lacking HO-1 develop progressive inflammatory diseases [9] and show enhanced sensitivity to lipopolysaccharide (LPS)-induced toxemia. HO-1 deficiency shows partial embryonic lethality.…”

mentioning

confidence: 99%

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Cytoprotective role of heme oxygenase-1 and heme degradation derived end products in liver injury

Origassa¹,

Câmara²

2013

WJH

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The activation of heme oxygenase-1 (HO-1) appears to be an endogenous defensive mechanism used by cells to reduce inflammation and tissue damage in a number of injury models. HO-1, a stress-responsive enzyme that catabolizes heme into carbon monoxide (CO), biliverdin and iron, has previously been shown to protect grafts from ischemia/reperfusion and rejection. In addition, the products of the HO-catalyzed reaction, particularly CO and biliverdin/bilirubin, have been shown to exert protective effects in the liver against a number of stimuli, as in chronic hepatitis C and in transplanted liver grafts. Furthermore, the induction of HO-1 expression can protect the liver against damage caused by a number of chemical compounds. More specifically, the CO derived from HO-1-mediated heme catabolism has been shown to be involved in the regulation of inflammation; furthermore, administration of REVIEW 541October 27, 2013|Volume 5|Issue 10| WJH|www.wjgnet.com low concentrations of exogenous CO has a protective effect against inflammation. Both murine and human HO-1 deficiencies have systemic manifestations associated with iron metabolism, such as hepatic overload (with signs of a chronic hepatitis) and iron deficiency anemia (with paradoxical increased levels of ferritin). Hypoxia induces HO-1 expression in multiple rodent, bovine and monkey cell lines, but interestingly, hypoxia represses expression of the human HO-1 gene in a variety of human cell types (endothelial cells, epithelial cells, T cells). These data suggest that HO-1 and CO are promising novel therapeutic molecules for patients with inflammatory diseases. In this review, we present what is currently known regarding the role of HO-1 in liver injuries and in particular, we focus on the implications of targeted induction of HO-1 as a potential therapeutic strategy to protect the liver against chemically induced injury.

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Section: Polymorphismssupporting

confidence: 79%

Section: Polymorphismsmentioning

confidence: 95%

Section: Regulation Of Ho-1mentioning

confidence: 99%

Section: Regulation Of Ho-1mentioning

confidence: 99%

mentioning

confidence: 99%

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Cytoprotective role of heme oxygenase-1 and heme degradation derived end products in liver injury

Origassa¹,

Câmara²

2013

WJH

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Anti-apoptotic therapeutic approaches in liver diseases: do they really make sense?

et al. 2014

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A variety of data suggesting apoptotic cell death as a key feature of liver injury stimulated researchers to investigate the therapeutic potential of anti-apoptotic strategies in experimental models. However, the overestimated role of apoptotic cell death in liver injury has tempered the clinical translation of the protection afforded by anti-apoptotic regimes in experimental models. Thus, the hope for apoptosis modulation as potential treatment strategy for injured liver in humans could not be confirmed. Herein, we evaluated the degree of apoptosis in different hepatic stress models which are relevant for the human pathophysiology. Using morphological criteria of apoptosis, caspase-3 activation as well as TUNEL assay in combination with a positive control of apoptosis in liver injury, we quantified apoptotic cell death discriminating between parenchymal and non-parenchymal cells and confirmed these results by cleaved caspase-3 and PARP-1 protein expression. Discussing our findings and relating them to the existing literature on the potential role of apoptotic cell death, we strongly recommend reconsidering anti-apoptotic strategies to ameliorate liver injury efficiently.

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Krill oil alleviates oxidative stress, iron accumulation and fibrosis in the liver and spleen of iron-overload rats

Helal

El‐Kashef

2019

Environ Sci Pollut Res

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Local interaction of apoptotic hepatocytes and Kupffer cells in a rat model of systemic endotoxemia

Abstract: With respect to the fundamental importance of cell apoptosis, improved knowledge of these cell-cell interactions might allow the development of new therapeutic strategies through the regulation of apoptotic cell death.

Cited by 14 publications

References 32 publications

Cytoprotective role of heme oxygenase-1 and heme degradation derived end products in liver injury

Cytoprotective role of heme oxygenase-1 and heme degradation derived end products in liver injury

Anti-apoptotic therapeutic approaches in liver diseases: do they really make sense?

Krill oil alleviates oxidative stress, iron accumulation and fibrosis in the liver and spleen of iron-overload rats

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