Chun Tang1, Heng Lin2, Qiao Wu2, Yujun Zhang2, Ping Bie3, Juntao Yang4. 1. Department of Hepatobiliary Surgery, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, Chongqing, China. 2. Department of Hepatobiliary Surgery, Institute of Hepatobiliary Surgery Southwest Hospital, The Third Military Medical University, Chongqing, China. 3. Department of Hepatobiliary Surgery, Institute of Hepatobiliary Surgery Southwest Hospital, The Third Military Medical University, Chongqing, China. Electronic address: medscibp@126.com. 4. Department of Hepatobiliary Surgery, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, Chongqing, China. Electronic address: juntaoyang2013@aliyun.com.
Abstract
BACKGROUND: Hepatocyte mitochondrial DNA (mtDNA) damage is an important cause of mitochondrial and hepatic function impairment in obstructive jaundice (OJ). This study investigated the protective effect of recombinant human augmenter of liver regeneration (rhALR) on hepatocyte mtDNA in rats with OJ. MATERIALS AND METHODS: Wistar rats were randomly divided into three groups as follows: sham-operation, biliary obstruction and recanalization with rhALR treatment (BDO-RBF-rhALR), and BDO-RBF-Vehicle (n = 48 per group). After biliary obstruction, rats were intraperitoneally injected with 40 μg/kg rhALR in BDO-RBF-rhALR group and same volume of normal saline in other two groups once every 12 h, until sacrifice. Mitochondrial transcription factor A (mtTFA) and nuclear respiratory factor-1 (NRF-1) expression in hepatocytes were detected by real-time reverse transcription-polymerase chain reaction and Western blot. Hepatocyte mtDNA damage was evaluated by real-time-polymerase chain reaction. Mitochondrial and hepatic functions were also assessed. RESULTS: After biliary obstruction, hepatic function was clearly impaired, as shown by the increases in serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels, and the decrease in albumin level. Mitochondrial respiratory control ratio, phosphorus oxygen ratio, and ATP levels (all indicators of mitochondrial function) were decreased. The relative amount of total mtDNA, mtTFA, and NRF-1 expression in rat liver tissues were decreased, whereas the relative amount of deleted mtDNA was increased. However, the damage was significantly improved in the BDO-RBF-rhALR group. After recanalization, these changes were gradually restored, but the recovery was faster in the BDO-RBF-rhALR group than in BDO-RBF-Vehicle group. CONCLUSIONS: rhALR may protect and improve mitochondrial and hepatic functions in rats with OJ by promoting the expression of mtTFA and NRF-1 and by protecting and repairing damaged mtDNA.
BACKGROUND: Hepatocyte mitochondrial DNA (mtDNA) damage is an important cause of mitochondrial and hepatic function impairment in obstructive jaundice (OJ). This study investigated the protective effect of recombinant human augmenter of liver regeneration (rhALR) on hepatocyte mtDNA in rats with OJ. MATERIALS AND METHODS:Wistar rats were randomly divided into three groups as follows: sham-operation, biliary obstruction and recanalization with rhALR treatment (BDO-RBF-rhALR), and BDO-RBF-Vehicle (n = 48 per group). After biliary obstruction, rats were intraperitoneally injected with 40 μg/kg rhALR in BDO-RBF-rhALR group and same volume of normal saline in other two groups once every 12 h, until sacrifice. Mitochondrial transcription factor A (mtTFA) and nuclear respiratory factor-1 (NRF-1) expression in hepatocytes were detected by real-time reverse transcription-polymerase chain reaction and Western blot. Hepatocyte mtDNA damage was evaluated by real-time-polymerase chain reaction. Mitochondrial and hepatic functions were also assessed. RESULTS: After biliary obstruction, hepatic function was clearly impaired, as shown by the increases in serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels, and the decrease in albumin level. Mitochondrial respiratory control ratio, phosphorus oxygen ratio, and ATP levels (all indicators of mitochondrial function) were decreased. The relative amount of total mtDNA, mtTFA, and NRF-1 expression in rat liver tissues were decreased, whereas the relative amount of deleted mtDNA was increased. However, the damage was significantly improved in the BDO-RBF-rhALR group. After recanalization, these changes were gradually restored, but the recovery was faster in the BDO-RBF-rhALR group than in BDO-RBF-Vehicle group. CONCLUSIONS: rhALR may protect and improve mitochondrial and hepatic functions in rats with OJ by promoting the expression of mtTFA and NRF-1 and by protecting and repairing damaged mtDNA.
Authors: C Tang; Y Hou; H Wang; K Wang; H Xiang; X Wan; Y Xia; J Li; W Wei; S Xu; Z Lei; T M Pawlik; H Wang; M Wu; F Shen Journal: Oncogenesis Date: 2017-07-17 Impact factor: 7.485