Intermittent ischaemia maintains function after ischaemia reperfusion in steatotic livers

Steenks, Mathilde; Baal, Mark C.P.M. van; Nieuwenhuijs, Vincent B.; Bruijn, Menno T. de; Schiesser, Marc; Teo, Mike H.; Callahan, Tom; Padbury, Rob; Barritt, Greg J.

doi:10.1111/j.1477-2574.2010.00160.x

Cited by 15 publications

(39 citation statements)

References 48 publications

(106 reference statements)

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“…) and were included in the analysis. Among the 18 studies, 13 examined the impact of IPC in warm IRI (http://onlinelibrary.wiley.com/doi/10.1111/hpb.12258/suppinfo, online) and the remaining five studies investigated the impact of IPC in cold IRI (http://onlinelibrary.wiley.com/doi/10.1111/hpb.12258/suppinfo, online). Experiments in all 18 studies had been carried out using male rodents and none had imposed any delay or interval between the IPC stimulus and the IRI episode.…”

Section: Resultsmentioning

confidence: 99%

“…Thirteen studies examined the effect of IPC on warm IRI in steatotic livers . The majority were performed in rats or mice ( n = 12) and one had used a rabbit model.…”

Section: Resultsmentioning

confidence: 99%

“…The majority were performed in rats or mice ( n = 12) and one had used a rabbit model. Eight studies used a genetic model of hepatic steatosis; four studies used dietary modifications so that steatosis was induced by either a choline‐deficient diet ( n = 2) or a high‐cholesterol diet ( n = 2) . One study had used both a genetic model ( ob/ob mouse) and choline‐deficient diet‐induced steatosis in C57 mice .…”

Section: Resultsmentioning

confidence: 99%

“…One study had used both a genetic model ( ob/ob mouse) and choline‐deficient diet‐induced steatosis in C57 mice . Eleven of the 13 studies had included both sham (laparotomy only) and non‐preconditioned steatotic livers as controls . The remaining two studies had used non‐preconditioned steatotic livers as control livers …”

Section: Resultsmentioning

confidence: 99%

“…Moderate‐to‐severe (> 30%) steatosis was present in 12 of the 13 studies . One study reported mild (< 30%) steatosis . Five studies investigated a predominance of macrovesicular steatosis (MaS), five studies examined mixed hepatic steatosis, two studies investigated a predominance of microvesicular steatosis (MiS) and one study investigated both types of steatosis independently.…”

Section: Resultsmentioning

confidence: 99%

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Impact of ischaemic preconditioning on experimental steatotic livers following hepatic ischaemia–reperfusion injury: a systematic review

Chu

Vather

Hickey

et al. 2015

HPB

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Section: Resultsmentioning

confidence: 99%

“…Thirteen studies examined the effect of IPC on warm IRI in steatotic livers . The majority were performed in rats or mice ( n = 12) and one had used a rabbit model.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

Impact of ischaemic preconditioning on experimental steatotic livers following hepatic ischaemia–reperfusion injury: a systematic review

Chu

Vather

Hickey

et al. 2015

HPB

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Increased expression of peroxiredoxin 1 and identification of a novel lipid‐metabolizing enzyme in the early phase of liver ischemia reperfusion injury

et al. 2011

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Warm ischemia reperfusion (IR) injury of the liver is associated with changes in the expression and/or post-translational modification of numerous proteins. Only a few of these have been identified. We used 2-D DIGE to identify cytosolic proteins altered in the early stage of IR in an established rat model of segmental hepatic ischemia. Proteins in 18 abundant spots altered by IR were identified by LC-MS/MS and Western blot. Many identified proteins were enzymes involved in glucose and lipid metabolism. Isoamyl acetate-hydrolysing esterase 1 homolog, not previously characterized in liver, was also identified. A threefold increase in peroxiredoxin 1 (Prx1) and its oxidized forms was observed as was an increase in Prx1 mRNA. Peroxiredoxins and their overoxidation have previously been associated with IR. In contrast to other studies, we did not detect typical overoxidation of Prx1 on the peroxidatic cysteine (Cys(52)). Instead, we identified novel overoxidation of the resolving cysteine (Cys(173)) residue by LC-MS/MS. Our results show that a rapid increase in Prx1 expression is associated with the early phase of IR of the liver, likely contributing to mechanisms that protect the liver against IR damage. Additionally, we have revealed a potential role in liver for a novel lipid-metabolizing enzyme.

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Metabolic Disorders and Cancer: Hepatocyte Store-Operated Ca2+ Channels in Nonalcoholic Fatty Liver Disease

Ali

Rychkov

Barritt

2017

Advances in Experimental Medicine and Biology

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In steatotic hepatocytes, intracellular Ca homeostasis is substantially altered compared to normal. Decreased Ca in the endoplasmic reticulum (ER) can lead to ER stress, an important mediator of the progression of liver steatosis to nonalcoholic steatohepatitis, type 2 diabetes, and hepatocellular carcinoma. Store-operated Ca channels (SOCs) in hepatocytes are composed principally of Orai1 and STIM1 proteins. Their main role is the maintenance of adequate Ca in the lumen of the ER. In steatotic hepatocytes, store-operated Ca entry (SOCE) is substantially inhibited. This inhibition is associated with a decrease in Ca in the ER. Lipid-induced inhibition of SOCE is mediated by protein kinase C (PKC) and may involve the phosphorylation and subsequent inhibition of Orai1. Experimental inhibition of SOCE enhances lipid accumulation in normal hepatocytes incubated in the presence of exogenous fatty acids. The antidiabetic drug exendin-4 reverses the lipid-induced inhibition of SOCE and decreases liver lipid with rapid onset. It is proposed that lipid-induced inhibition of SOCE in the plasma membrane and of SERCA2b in the ER membrane leads to a persistent decrease in ER Ca, ER stress, and the ER stress response, which in turn enhances (amplifies) lipid accumulation. A low level of persistent SOCE due to chronic ER Ca depletion in steatotic hepatocytes may contribute to an elevated cytoplasmic-free Ca concentration leading to the activation of calcium-calmodulin kinase II (CaMKII), decreased lipid removal by autophagy, and insulin resistance. It is concluded that lipid-induced inhibition of SOCE plays an important role in the progression of liver steatosis to insulin insensitivity and hepatocellular carcinoma.

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Intermittent ischaemia maintains function after ischaemia reperfusion in steatotic livers

Abstract: INT is more effective than IPC in restoring liver function in the acute phase of IR in steatotic livers. In obese patients, INT may be useful in promoting better liver function after IR after liver resection.

Cited by 15 publications

References 48 publications

Impact of ischaemic preconditioning on experimental steatotic livers following hepatic ischaemia–reperfusion injury: a systematic review

Impact of ischaemic preconditioning on experimental steatotic livers following hepatic ischaemia–reperfusion injury: a systematic review

Increased expression of peroxiredoxin 1 and identification of a novel lipid‐metabolizing enzyme in the early phase of liver ischemia reperfusion injury

Metabolic Disorders and Cancer: Hepatocyte Store-Operated Ca2+ Channels in Nonalcoholic Fatty Liver Disease

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