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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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Morphological alterations in liver mitochondria during ALF. Control group, the mitochondria were round or oval with complete membrane structures and concentric circles or longitudinally arranged ridges that were tidy and compact; ALF 4 h, the mitochondria were reduced in number, fairly structured, relatively complete and had a complete structure of ridges that had a relatively tidy arrangement but with concentrated stroma; ALF 8 h, the mitochondria were swollen and clearly damaged but had somewhat complete outer membranes and disorganized ridge structures; ALF 12 h, the mitochondria were clearly swollen and their inner structures were not easily visible; ALF 24 h, the outer membrane was disrupted and the mitochondria had collapsed. ALF, acute liver failure.
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f3-mmr-12-04-5035: Morphological alterations in liver mitochondria during ALF. Control group, the mitochondria were round or oval with complete membrane structures and concentric circles or longitudinally arranged ridges that were tidy and compact; ALF 4 h, the mitochondria were reduced in number, fairly structured, relatively complete and had a complete structure of ridges that had a relatively tidy arrangement but with concentrated stroma; ALF 8 h, the mitochondria were swollen and clearly damaged but had somewhat complete outer membranes and disorganized ridge structures; ALF 12 h, the mitochondria were clearly swollen and their inner structures were not easily visible; ALF 24 h, the outer membrane was disrupted and the mitochondria had collapsed. ALF, acute liver failure.

Mentions: The hepatocyte mitochondria from the control group were round or oval with complete membrane structures and concentric circles or longitudinally arranged ridges that were tidy and compact. In the ALF 4 h group, the mitochondria were reduced in number, fairly structured, fairly complete and had a complete structure of ridges that had a fairly tidy arrangement but with concentrated stroma. In the ALF 8 h group, the mitochondria were swollen and clearly damaged but had somewhat complete outer membranes and disorganized ridge structures. In the ALF 12 h group, the mitochondria were swollen and their inner structures were not easily visible. In the ALF 24 h group, the outer membrane was disrupted and the mitochondria had collapsed (Fig. 3).


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)

Morphological alterations in liver mitochondria during ALF. Control group, the mitochondria were round or oval with complete membrane structures and concentric circles or longitudinally arranged ridges that were tidy and compact; ALF 4 h, the mitochondria were reduced in number, fairly structured, relatively complete and had a complete structure of ridges that had a relatively tidy arrangement but with concentrated stroma; ALF 8 h, the mitochondria were swollen and clearly damaged but had somewhat complete outer membranes and disorganized ridge structures; ALF 12 h, the mitochondria were clearly swollen and their inner structures were not easily visible; ALF 24 h, the outer membrane was disrupted and the mitochondria had collapsed. ALF, acute liver failure.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3-mmr-12-04-5035: Morphological alterations in liver mitochondria during ALF. Control group, the mitochondria were round or oval with complete membrane structures and concentric circles or longitudinally arranged ridges that were tidy and compact; ALF 4 h, the mitochondria were reduced in number, fairly structured, relatively complete and had a complete structure of ridges that had a relatively tidy arrangement but with concentrated stroma; ALF 8 h, the mitochondria were swollen and clearly damaged but had somewhat complete outer membranes and disorganized ridge structures; ALF 12 h, the mitochondria were clearly swollen and their inner structures were not easily visible; ALF 24 h, the outer membrane was disrupted and the mitochondria had collapsed. ALF, acute liver failure.
Mentions: The hepatocyte mitochondria from the control group were round or oval with complete membrane structures and concentric circles or longitudinally arranged ridges that were tidy and compact. In the ALF 4 h group, the mitochondria were reduced in number, fairly structured, fairly complete and had a complete structure of ridges that had a fairly tidy arrangement but with concentrated stroma. In the ALF 8 h group, the mitochondria were swollen and clearly damaged but had somewhat complete outer membranes and disorganized ridge structures. In the ALF 12 h group, the mitochondria were swollen and their inner structures were not easily visible. In the ALF 24 h group, the outer membrane was disrupted and the mitochondria had collapsed (Fig. 3).

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