Oxidative injury and hepatocyte apoptosis in total parenteral nutrition–associated liver dysfunction

Cai, Wei; Wu, Jiang; Hong, Li; Xu, Yuanfei; Tang, Qingya; Shi, Cheng-ren

doi:10.1016/j.jpedsurg.2006.05.067

Cited by 40 publications

(38 citation statements)

References 19 publications

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 86%

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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“…The cytosolic concentration of choline, a critical nutrient for lipoprotein secretion, also decreases, promoting lipid storage in hepatocytes [Allard, 2002]. The duration of TPN administration correlates with the severity of liver injury and in rare cases can result in end-stage liver disease [Cai et al 2006]. The predominant histologic findings are steatosis, intrahepatic cholestasis, and ductular reduplication (Figure 1).…”

Section: Nutritional Causesmentioning

confidence: 99%

Secondary causes of nonalcoholic fatty liver disease

Kneeman

Misdraji

Corey

2011

Therap Adv Gastroenterol

227

195

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Nonalcoholic fatty liver disease (NAFLD) is becoming the most common cause of chronic liver disease in the developing world, found in 17-30% of the population in Western countries and 2-4% worldwide. Defined as the accumulation of fatty acid content greater than 5% of liver weight, NAFLD is a spectrum of disease ranging from simple steatosis to nonalcoholic steatohepatitis. The pathophysiology of NAFLD involves increased de novo synthesis of fatty acids in hepatocytes, the retention of lipids due to impaired hepatocyte apolipoprotein secretion or beta-oxidation. The well-known primary causes of NAFLD are obesity, type II diabetes, dyslipidemia, and insulin resistance. However, other less common conditions can cause a similar clinical and histologic picture, and should be considered in patients who present with NAFLD but do not have traditional risk factors. In this review, we discuss uncommon but important causes of NAFLD, including inborn errors of metabolism, iatrogenic causes, viral hepatitis, and nutritional disorders to provide practicing clinicians with an understanding of the less well recognized causes of NAFLD.

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“…Conversely, the products of oxidative injury are increased [ 84 ]. Oxidative injury and subsequent hepatocyte apoptosis also play a role in PNLD [ 85 ]. Nutrient defi ciencies, such as choline, glutamine, and taurine, may also contribute to the development of PNLD [ 28 , 86 , 87 ].…”

Section: Intrahepatic Complicationsmentioning

confidence: 99%

Cholestasis in the Hospitalized Patient

Larson

2014

Clinical Gastroenterology

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Oxidative injury and hepatocyte apoptosis in total parenteral nutrition–associated liver dysfunction

Cited by 40 publications

References 19 publications

Palmitate Induces TRB3 Expression and Promotes Apoptosis in Human Liver Cells

Palmitate Induces TRB3 Expression and Promotes Apoptosis in Human Liver Cells

Secondary causes of nonalcoholic fatty liver disease

Cholestasis in the Hospitalized Patient

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