Chinese Journal of Physiology

ORIGINAL ARTICLE
Year
: 2020  |  Volume : 63  |  Issue : 2  |  Page : 68--76

Repetitively hypoxic preconditioning attenuates ischemia/reperfusion-induced liver dysfunction through upregulation of hypoxia-induced factor-1 alpha-dependent mitochondrial Bcl-xl in rat


Pei-Lei Chou1, Kuo-Hsin Chen2, Tzu-Ching Chang1, Chiang-Ting Chien1 
1 School of Life Science, National Taiwan Normal University, Taipei, Taiwan
2 Department of Surgery, Division of General Surgery, Far-Eastern Memorial Hospital; Department of Electrical Engineering, Yuan Ze University, Taoyuan City, Taiwan

Correspondence Address:
Prof. Chiang-Ting Chien
No. 88, Sec. 4, Tingzhou Road, School of Life Science, National Taiwan Normal University, Taipei 11677
Taiwan
Prof. Tzu-Ching Chang
No. 88, Sec. 4, Tingzhou Road, School of Life Science, National Taiwan Normal University, Taipei 11677
Taiwan

Repetitive hypoxic preconditioning (HP) enforces protective effects to subsequently severe hypoxic/ischemic stress. We hypothesized that HP may provide protection against ischemia/reperfusion (I/R) injury in rat livers via hypoxia-induced factor-1 alpha (HIF-1α)/reactive oxygen species (ROS)-dependent defensive mechanisms. Female Wistar rats were exposed to hypoxia (15 h/day) in a hypobaric hypoxic chamber (5500 m) for HP induction, whereas the others were kept in sea level. These rats were subjected to 45 min of hepatic ischemia by portal vein occlusion followed by 6 h of reperfusion. We evaluated HIF-1α in nuclear extracts, MnSOD, CuZnSOD, catalase, Bad/Bcl-xL/caspase 3/poly-(ADP-ribose)-polymerase (PARP), mitochondrial Bcl-xL, and cytosolic cytochrome C expression with Western blot and nitroblue tetrazolium/3-nitrotyrosine stain. Kupffer cell infiltration and terminal deoxynucleotidyl transferase-mediated nick-end labeling method apoptosis were determined by immunocytochemistry. The ROS value from liver surface and bile was detected by an ultrasensitive chemiluminescence–amplification method. Hepatic function was assessed with plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. HP increased nuclear translocation of HIF-1α and enhanced Bcl-xL, MnSOD, CuZnSOD, and catalase protein expression in a time-dependent manner. The response of HP enhanced hepatic HIF-1α, and Bcl-xL expression was abrogated by a HIF-1α inhibitor YC-1. Hepatic I/R increased ROS levels, myeloperoxidase activity, Kupffer cell infiltration, ALT and AST levels associated with the enhancement of cytosolic Bad translocation to mitochondria, release of cytochrome C to cytosol, and activation of caspase 3/PARP-mediated apoptosis. HP significantly ameliorated hepatic I/R-enhanced oxidative stress, apoptosis, and mitochondrial and hepatic dysfunction. In summary, HP enhances HIF-1α/ROS-dependent cascades to upregulate mitochondrial Bcl-xL protein expression and to confer protection against I/R injury in the livers.


How to cite this article:
Chou PL, Chen KH, Chang TC, Chien CT. Repetitively hypoxic preconditioning attenuates ischemia/reperfusion-induced liver dysfunction through upregulation of hypoxia-induced factor-1 alpha-dependent mitochondrial Bcl-xl in rat.Chin J Physiol 2020;63:68-76


How to cite this URL:
Chou PL, Chen KH, Chang TC, Chien CT. Repetitively hypoxic preconditioning attenuates ischemia/reperfusion-induced liver dysfunction through upregulation of hypoxia-induced factor-1 alpha-dependent mitochondrial Bcl-xl in rat. Chin J Physiol [serial online] 2020 [cited 2021 Jun 22 ];63:68-76
Available from: https://www.cjphysiology.org/article.asp?issn=0304-4920;year=2020;volume=63;issue=2;spage=68;epage=76;aulast=Chou;type=0