Heme oxygenase-1 protects human hepatocytes in vitro against warm and cold hypoxia

Tuzuner, E. D. A.; Liu, Liegang; Shimada, Masashi; Yılmaz, Esra Karabağ; Glanemann, Matthias; Settmacher, Utz; Langrehr, Jan M.; Jonas, Sven; Neuhaus, P.; Nüssler, Andreas K.

doi:10.1016/j.jhep.2004.07.013

Cited by 23 publications

(10 citation statements)

References 40 publications

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“…4). These results are in agreement with other studies with human hepatocytes, cardiomyocytes and mesenchymal cells31. We also observed that Caco-2 cells in normoxia produced 63% more LDH than hepatocytes.…”

Section: Discussionsupporting

confidence: 94%

HYPOXIC STRESS, HEPATOCYTES AND CACO-2 VIABILITY AND SUSCEPTIBILITY TO Shigella flexneri INVASION

Lima

Santos

Andrade

2013

Rev. Inst. Med. trop. S. Paulo

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SUMMARYInflammation due to Shigella flexneri can cause damage to the colonic mucosa and cell death by necrosis and apoptosis. This bacteria can reach the bloodstream in this way, and the liver through portal veins. Hypoxia is a condition present in many human diseases, and it may induce bacterial translocation from intestinal lumen. We studied the ability of S. flexneri to invade rat hepatocytes and Caco-2 cells both in normoxic and hypoxic microenvironments, as well as morphological and physiological alterations in these cells after infection under hypoxia. We used the primary culture of rat hepatocytes as a model of study. We analyzed the following parameters in normoxic and hypoxic conditions: morphology, cell viability, bacterial recovery and lactate dehydrogenase (LDH) released. The results showed that there were fewer bacteria within the Caco-2 cells than in hepatocytes in normoxic and hypoxic conditions. We observed that the higher the multiplicity of infection (MOI) the greater the bacterial recovery in hepatocytes. The hypoxic condition decreased the bacterial recovery in hepatocytes. The cytotoxicity evaluated by LDH released by cells was significantly higher in cells submitted to hypoxia than normoxia. Caco-2 cells in normoxia released 63% more LDH than hepatocytes. LDH increased 164% when hepatocytes were submitted to hypoxia and just 21% when Caco-2 cells were in the same condition. The apoptosis evaluated by Tunel was significantly higher in cells submitted to hypoxia than normoxia. When comparing hypoxic cells, we obtained more apoptotic hepatocytes than apoptotic Caco-2 cells. Concluding our results contribute to a better knowledge of interactions between studied cells and Shigella flexneri. These data may be useful in the future to define strategies to combat this virulent pathogen.

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Section: Discussionsupporting

confidence: 94%

HYPOXIC STRESS, HEPATOCYTES AND CACO-2 VIABILITY AND SUSCEPTIBILITY TO Shigella flexneri INVASION

Lima

Santos

Andrade

2013

Rev. Inst. Med. trop. S. Paulo

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“…Such regulation of these genes was apparent in these observations: only the induction of the HO-1 and MT-2 isoforms changed considerably, with the induction level dependent on the stimulus applied. As concerns HO-1, its increased expression is regarded as a sign of the activation of an endogenous protective reaction in response to oxidative stress (Tüzüner et al, 2004). In our study, a moderately increased induction of hepatic HO-1 was observed even as late as 3 days after the biliary obstruction.…”

Section: Discussionsupporting

confidence: 58%

Effects of Kupffer cell blockade on the hepatic expression of metallothionein and heme oxygenase genes in endotoxemic rats with obstructive jaundice

et al. 2012

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“…Therefore, HO-1 induction has been suggested to have a general adaptive response and enhanced resistance to various stresses (30,35,37). Accordingly, pharmacological activation of HO-1 is a novel therapeutic intervention for various diseases involved in oxidative stress (2,3).…”

Section: Discussionmentioning

confidence: 99%

The protective role of HO-1 and its generated products (CO, bilirubin, and Fe) in ethanol-induced human hepatocyte damage

Yao¹,

Hao²,

Nüssler³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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It has been reported that naturally occurring quercetin exerts hepatoprotective effects through heme oxygenase-1 (HO-1) induction. However, the precise mechanism of how ethanol-associated liver damage is counteracted by quercetin-enhanced HO-1 metabolism still remains unclear. To further decipher the protective role of quercetin on ethanol-induced liver damage, we treated human hepatocytes with quercetin and various (end) products of the HO-1 pathway. Our data clearly showed that quercetin treatment attenuated ethanol-induced damage, whereas hemoglobin and zinc protoporphyrin 9 (ZnPP) abolished such effects. Iron-II aggravated ethanol toxicity and was only partially reduced by quercetin. In contrast, carbon monoxide (CO) dose dependently inhibited ethanol-induced cytochrome P450 2E1 (CYP 2E1) activity and hepatotoxicity but had no influence on CYP 2E1 protein expression. Similarly, hemoglobin dramatically stimulated CYP 2E1 activity but not the protein expression in quercetin- and ethanol-cotreated hepatocytes. ZnPP significantly promoted CYP 2E1 protein expression in the presence and absence of CO treatment but inhibited ethanol-induced CYP 2E1 activation following CO incubation in quercetin- and ethanol-cotreated hepatocytes. These results suggested that quercetin virtually attenuated ethanol-derived oxidative damage via HO-1 induction. Heme degradation and CO release may mediate the protective effects through inhibiting ethanol-induced CYP 2E1 synthesis and enzymatic activity, respectively.

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Heme oxygenase-1 protects human hepatocytes in vitro against warm and cold hypoxia

Cited by 23 publications

References 40 publications

HYPOXIC STRESS, HEPATOCYTES AND CACO-2 VIABILITY AND SUSCEPTIBILITY TO Shigella flexneri INVASION

HYPOXIC STRESS, HEPATOCYTES AND CACO-2 VIABILITY AND SUSCEPTIBILITY TO Shigella flexneri INVASION

Effects of Kupffer cell blockade on the hepatic expression of metallothionein and heme oxygenase genes in endotoxemic rats with obstructive jaundice

The protective role of HO-1 and its generated products (CO, bilirubin, and Fe) in ethanol-induced human hepatocyte damage

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