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Promotion of mitochondrial energy metabolism during hepatocyte apoptosis in a rat model of acute liver failure.

Chen LY, Yang B, Zhou L, Ren F, Duan ZP, Ma YJ - Mol Med Rep (2015)

Bottom Line: Hepatocyte necrosis appeared at 12 h and was significantly higher at 24 h with inflammatory cell invasion.Therefore, these results demonstrated that energy metabolism is important in hepatocyte apoptosis during ALF and hepatocyte apoptosis is an active and energy‑consuming procedure.The current study on how hepatocyte energy metabolism affects the transmission of death signals may provide a basis for the early diagnosis and development of an improved therapeutic strategy for ALF.

View Article: PubMed Central - PubMed

Affiliation: The Second Department of Infectious Diseases, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.

ABSTRACT
Hepatocyte apoptosis and energy metabolism in mitochondria have an important role in the mechanism of acute liver failure (ALF). However, data on the association between apoptosis and the energy metabolism of hepatocytes are lacking. The current study assessed the activity of several key enzymes in mitochondria during ALF, including citrate synthase (CS), carnitine palmitoyltransferase‑1 (CPT‑1) and cytochrome c oxidase (COX), which are involved in hepatocyte energy metabolism. A total of 40 male Sprague‑Dawley rats were divided into five groups and administered D‑galactosamine and lipopolysaccharide to induce ALF. Hepatic pathology and terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling examinations indicated that hepatocyte apoptosis was observed at 4 h and increased 8 h after ALF. Hepatocyte necrosis appeared at 12 h and was significantly higher at 24 h with inflammatory cell invasion. The results measured by electron microscopy indicated that ultrastructural changes in mitochondria began at 4 h and the mitochondrial outer membrane was completely disrupted at 24 h resulting in mitochondrial collapse. The expression of CS, CPT‑1 and COX was measured and analyzed using assay kits. The activity and protein expression of CS, CPT‑1 and COX began to increase at 4 h, reached a peak at 8 h and decreased at 12 h during ALF. The activities of CS, CPT‑1 and COX were enhanced during hepatocyte apoptosis suggesting that these enzymes are involved in the initiation and development of ALF. Therefore, these results demonstrated that energy metabolism is important in hepatocyte apoptosis during ALF and hepatocyte apoptosis is an active and energy‑consuming procedure. The current study on how hepatocyte energy metabolism affects the transmission of death signals may provide a basis for the early diagnosis and development of an improved therapeutic strategy for ALF.

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Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling detection of apoptosis in rat livers during the early stages of ALF. (A–C) Apoptotic cells were visible 4 and 8 h after D-galactosamine/lipopolysaccharide treatment in rats and were located predominantly around the central vein, as indicated by arrows; (D) 10 fields of view were randomly selected from sections of every sample and the apoptotic cells were counted under a lens (magnification, ×200) to calculate the number of apoptotic cells in every 100 cells. ALF, acute liver failure.
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f2-mmr-12-04-5035: Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling detection of apoptosis in rat livers during the early stages of ALF. (A–C) Apoptotic cells were visible 4 and 8 h after D-galactosamine/lipopolysaccharide treatment in rats and were located predominantly around the central vein, as indicated by arrows; (D) 10 fields of view were randomly selected from sections of every sample and the apoptotic cells were counted under a lens (magnification, ×200) to calculate the number of apoptotic cells in every 100 cells. ALF, acute liver failure.

Mentions: TUNEL staining demonstrated that cellular injury occurred predominantly in an apoptotic pattern during the early stages of ALF. As shown in (Fig. 2A–C), apoptotic cells were predominantly located around the central vein and were characterized by their shrunken, round shape, small cell body, concentrated cytoplasm, increased density of nuclear chromatin, which congregated near the nuclear membrane, and their invaginated cellular membrane, which separated the cell into membrane-encapsulated apoptotic bodies varying in size. The AI was significantly different between the control group (10.60±2.61), ALF 4 h (48.90±10.76) and ALF 8 h groups (74.60±14.85; Fig. 2D).


Promotion of mitochondrial energy metabolism during hepatocyte apoptosis in a rat model of acute liver failure.

Chen LY, Yang B, Zhou L, Ren F, Duan ZP, Ma YJ - Mol Med Rep (2015)

Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling detection of apoptosis in rat livers during the early stages of ALF. (A–C) Apoptotic cells were visible 4 and 8 h after D-galactosamine/lipopolysaccharide treatment in rats and were located predominantly around the central vein, as indicated by arrows; (D) 10 fields of view were randomly selected from sections of every sample and the apoptotic cells were counted under a lens (magnification, ×200) to calculate the number of apoptotic cells in every 100 cells. ALF, acute liver failure.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581801&req=5

f2-mmr-12-04-5035: Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling detection of apoptosis in rat livers during the early stages of ALF. (A–C) Apoptotic cells were visible 4 and 8 h after D-galactosamine/lipopolysaccharide treatment in rats and were located predominantly around the central vein, as indicated by arrows; (D) 10 fields of view were randomly selected from sections of every sample and the apoptotic cells were counted under a lens (magnification, ×200) to calculate the number of apoptotic cells in every 100 cells. ALF, acute liver failure.
Mentions: TUNEL staining demonstrated that cellular injury occurred predominantly in an apoptotic pattern during the early stages of ALF. As shown in (Fig. 2A–C), apoptotic cells were predominantly located around the central vein and were characterized by their shrunken, round shape, small cell body, concentrated cytoplasm, increased density of nuclear chromatin, which congregated near the nuclear membrane, and their invaginated cellular membrane, which separated the cell into membrane-encapsulated apoptotic bodies varying in size. The AI was significantly different between the control group (10.60±2.61), ALF 4 h (48.90±10.76) and ALF 8 h groups (74.60±14.85; Fig. 2D).

Bottom Line: Hepatocyte necrosis appeared at 12 h and was significantly higher at 24 h with inflammatory cell invasion.Therefore, these results demonstrated that energy metabolism is important in hepatocyte apoptosis during ALF and hepatocyte apoptosis is an active and energy‑consuming procedure.The current study on how hepatocyte energy metabolism affects the transmission of death signals may provide a basis for the early diagnosis and development of an improved therapeutic strategy for ALF.

View Article: PubMed Central - PubMed

Affiliation: The Second Department of Infectious Diseases, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.

ABSTRACT
Hepatocyte apoptosis and energy metabolism in mitochondria have an important role in the mechanism of acute liver failure (ALF). However, data on the association between apoptosis and the energy metabolism of hepatocytes are lacking. The current study assessed the activity of several key enzymes in mitochondria during ALF, including citrate synthase (CS), carnitine palmitoyltransferase‑1 (CPT‑1) and cytochrome c oxidase (COX), which are involved in hepatocyte energy metabolism. A total of 40 male Sprague‑Dawley rats were divided into five groups and administered D‑galactosamine and lipopolysaccharide to induce ALF. Hepatic pathology and terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling examinations indicated that hepatocyte apoptosis was observed at 4 h and increased 8 h after ALF. Hepatocyte necrosis appeared at 12 h and was significantly higher at 24 h with inflammatory cell invasion. The results measured by electron microscopy indicated that ultrastructural changes in mitochondria began at 4 h and the mitochondrial outer membrane was completely disrupted at 24 h resulting in mitochondrial collapse. The expression of CS, CPT‑1 and COX was measured and analyzed using assay kits. The activity and protein expression of CS, CPT‑1 and COX began to increase at 4 h, reached a peak at 8 h and decreased at 12 h during ALF. The activities of CS, CPT‑1 and COX were enhanced during hepatocyte apoptosis suggesting that these enzymes are involved in the initiation and development of ALF. Therefore, these results demonstrated that energy metabolism is important in hepatocyte apoptosis during ALF and hepatocyte apoptosis is an active and energy‑consuming procedure. The current study on how hepatocyte energy metabolism affects the transmission of death signals may provide a basis for the early diagnosis and development of an improved therapeutic strategy for ALF.

Show MeSH
Related in: MedlinePlus