Mitochondria-initiated apoptosis triggered by oxidative injury play a role in total parenteral nutrition–associated liver dysfunction in infant rabbit model

Hong, Li; Wang, Xiang; Wu, Jiang; Cai, Wei

doi:10.1016/j.jpedsurg.2009.04.002

Cited by 24 publications

(21 citation statements)

References 31 publications

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“…Recently, we and others have reported that oxidative stress is involved in TPN-induced liver injuries in infants due to their immature antioxidant systems. [8][9][10][11] . However, the mechanisms of oxidative stress-mediated TPN-associated liver injury remains poorly understood and few approaches have been developed to prevent complications from TPN.…”

Section: Discussionmentioning

confidence: 99%

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RETRACTED ARTICLE: p38/p53/miR-200a-3p feedback loop promotes oxidative stress-mediated liver cell death

Xiao

Yan

et al. 2015

Cell Cycle

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Although our previous studies have provided evidence that oxidative stress has an essential role in total parenteral nutrition (TPN)-associated liver injury, the mechanisms involved are incompletely understood. Here, we show the existence of crosstalk between the miR-200 family of microRNAs and oxidative stress. The members of the miR-200 family are markedly enhanced in hepatic cells by hydrogen peroxide (H2O2) treatment. The upregulation of miR-200-3p in turn modulates the H2O2-mediated oxidative stress response by targeting p38α. The enhanced expression of miR-200-3p mimics p38α deficiency and promotes H2O2-induced cell death. Members of the miR-200 family that are known to inhibit the epithelial to mesenchymal transition (EMT) are induced by the tumor suppressor p53. Here, we show that p53 phosphorylation at Ser 33 contributes to H2O2-induced miR-200s transcription. In addition, we show that p38α can directly phosphorylate p53 at serine 33 upon H2O2 exposure. Thus, we suggest that in liver cells, the oxidative stress-induced, p38α-mediated phosphorylation of p53 at Ser33 is essential for the functional regulation of oxidative stress-induced miR-200 transcription by p53. Collectively, our data indicate that the p53-dependent expression of miR-200a-3p promotes cell death by inhibiting a p38/p53/miR-200 feedback loop.

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Section: Discussionmentioning

confidence: 99%

“…Peroxides in TPN are derived mainly from the reduction of vitamins 4 , lipid emulsions 5 , interactions between nutrients and ambient light 6 and dissolving oxygen that generates hydrogen peroxide 7,[8][9][10][11] .…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: p38/p53/miR-200a-3p feedback loop promotes oxidative stress-mediated liver cell death

Xiao

Yan

et al. 2015

Cell Cycle

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“…While there is compelling evidence to indicate that hepatocyte lipotoxicity and apoptosis is the cause of PNALD [9,10], a definitive mechanism remains unclear. We speculate that ER stress-dependent apoptosis may be involved in the pathogenesis of PNALD, and that the effect of TRB3 on the ATF4/CHOP and Akt pathway may be part of the molecular mechanism underlying PNALD.…”

Section: Discussionmentioning

confidence: 99%

“…It was shown that TRB3 can be induced in the liver by various stressors in vivo [24,25,26]. We have previously reported that oxidative injury and hepatocyte apoptosis might play an important role in the pathogenesis of PNALD [9,10]. Given the association between TRB3 and ER stress, we hypothesize that TRB3 is an important regulator of palmitate-induced apoptosis in human liver cells and might be involved in pathogenesis of PNALD.…”

Section: Introductionmentioning

confidence: 86%

“…For example, intravenous lipid emulsions, particularly phytosterols, have been implicated in the development of PNALD [1,2,3,5]. It is generally accepted that accumulation of lipids in the liver can lead to lipotoxicity and apoptosis, which were demonstrated to be involved in PNALD [6,7,8,9,10]. Nevertheless, the exact molecular mechanism of apoptosis induced by lipid accumulation is unknown.…”

Section: Introductionmentioning

confidence: 99%

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Palmitate Induces TRB3 Expression and Promotes Apoptosis in Human Liver Cells

Yan

Wang

Xiao

et al. 2014

Cell Physiol Biochem

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Background/Aims: Parenteral nutrition-associated liver disease (PNALD) is a major complication for patients who require long-term parenteral nutrition. Treatment options for PNALD are limited and its pathogenesis is poorly understood. Tribbles homolog 3 (TRB3) is a pseudokinase that modulates many signal transduction cascades and may be involved in the pathogenesis of PNALD. The aim of this study was to examine the role of TRB3 in palmitate-induced endoplasmic reticulum (ER) stress, in the human liver cell line L02. Methods: L02 cells were treated with palmitate, and its effect on cell viability, mitochondrial membrane potential, apoptosis and TRB3 expression were assessed. The role of TRB3 was also studied using transient overexpression of TRB3 in L02 cells, as well as its interaction with Akt signaling. Results: We found that palmitate induced ER stress and apoptosis in L02 cells. Palmitate-associated ER stress was accompanied by a significant induction of TRB3 expression at the mRNA and protein level. Overexpression of TRB3 potentiated the deleterious effects of palmitate, which was associated with decreased levels of phospho-Akt. Conclusions: TRB3 is an important mediator of palmitate-induced apoptosis in human liver cells, suggesting that it may also be involved in the molecular mechanism underlying PNALD.

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Novel Strategies to Prevent Total Parenteral Nutrition‐Induced Gut and Liver Inflammation, and Adverse Metabolic Outcomes

Lucchinetti

Lou

Wawrzyniak

et al. 2020

Molecular Nutrition Food Res

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Total parenteral nutrition (TPN) is a life‐saving therapy administered to millions of patients. However, it is associated with significant adverse effects, namely liver injury, risk of infections, and metabolic derangements. In this review, the underlying causes of TPN‐associated adverse effects, specifically gut atrophy, dysbiosis of the intestinal microbiome, leakage of the epithelial barrier with bacterial invasion, and inflammation are first described. The role of the bile acid receptors farnesoid X receptor and Takeda G protein‐coupled receptor, of pleiotropic hormones, and growth factors is highlighted, and the mechanisms of insulin resistance, namely the lack of insulinotropic and insulinomimetic signaling of gut‐originating incretins as well as the potentially toxicity of phytosterols and pro‐inflammatory fatty acids mainly released from soybean oil‐based lipid emulsions, are discussed. Finally, novel approaches in the design of next generation lipid delivery systems are proposed. Propositions include modifying the physicochemical properties of lipid emulsions, the use of lipid emulsions generated from sustainable oils with favorable ratios of anti‐inflammatory n‐3 to pro‐inflammatory n‐6 fatty acids, beneficial adjuncts to TPN, and concomitant pharmacotherapies to mitigate TPN‐associated adverse effects.

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Mitochondria-initiated apoptosis triggered by oxidative injury play a role in total parenteral nutrition–associated liver dysfunction in infant rabbit model

Cited by 24 publications

References 31 publications

RETRACTED ARTICLE: p38/p53/miR-200a-3p feedback loop promotes oxidative stress-mediated liver cell death

RETRACTED ARTICLE: p38/p53/miR-200a-3p feedback loop promotes oxidative stress-mediated liver cell death

Palmitate Induces TRB3 Expression and Promotes Apoptosis in Human Liver Cells

Novel Strategies to Prevent Total Parenteral Nutrition‐Induced Gut and Liver Inflammation, and Adverse Metabolic Outcomes

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