Excessive l-cysteine induces vacuole-like cell death by activating endoplasmic reticulum stress and mitogen-activated protein kinase signaling in intestinal porcine epithelial cells

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• 作者：Yun Ji ; Zhenlong Wu ; Zhaolai Dai ; Kaiji Sun ; Qing Zhang ; Guoyao Wu
• 关键词：l ; Cysteine ; Intestinal epithelial cells ; Endoplasmic reticulum stress ; Mitogen ; activated protein kinase ; Cell death
• 刊名：Amino Acids
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：48
• 期：1
• 页码：149-156
• 全文大小：1,295 KB
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• 作者单位：Yun Ji (1)
  Zhenlong Wu (1)
  Zhaolai Dai (1)
  Kaiji Sun (1)
  Qing Zhang (1)
  Guoyao Wu (1) (2)
  
  1. State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, China Agricultural University, 100193, Beijing, China
  2. Department of Animal Science, Texas A&M University, College Station, TX, 77843, USA
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Biochemistry
  Analytical Chemistry
  Biochemical Engineering
  Life Sciences
  Proteomics
  Neurobiology
  
• 出版者：Springer Wien
• ISSN：1438-2199

文摘

High intake of dietary cysteine is extremely toxic to animals and the underlying mechanism remains largely unknown. This study was conducted to test the hypothesis that excessive l-cysteine induces cell death by activating endoplasmic reticulum (ER) stress and mitogen-activated protein kinase (MAPK) signaling in intestinal porcine epithelial cells. Jejunal enterocytes were cultured in the presence of 0–10 mmol/L l-cysteine. Cell viability, morphologic alterations, mRNA levels for genes involved in ER stress, protein abundances for glucose-regulated protein 78, C/EBP homologous protein (CHOP), alpha subunit of eukaryotic initiation factor-2 (eIF2α), extracellular signal-regulated kinase (ERK1/2), p38 MAPK, and c-Jun N-terminal protein kinase (JNK1/2) were determined. The results showed that l-cysteine (5–10 mmol/L) reduced cell viability (P < 0.05) and led to vacuole-like cell death in intestinal porcine epithelial cells. These adverse effects of L-cysteine  were not affected by the autophagy inhibitor 3-methyladenine. The protein abundances for CHOP, phosphorylated (p)-eIF2α, p-JNK1/2, p-p38 MAPK, and the spliced form of XBP-1 mRNA were enhanced (P < 0.05), whereas those for p-ERK1/2 were reduced (P < 0.05). Collectively,  excessive  l-cysteine induces vacuole-like cell death via the  activation of ER stress and MAPK signaling in small intestinal epithelial cells. These signaling pathways may be potential targets for developing effective strategies to prevent the toxicity of dietary cysteine. Keywords l-Cysteine Intestinal epithelial cells Endoplasmic reticulum stress Mitogen-activated protein kinase Cell death