Cold-induced apoptosis of rat liver endothelial cells: Contribution of mitochondrial alterations

被引:37
作者
Kerkweg, U
Jacob, M
de Groot, H
Mannherz, HG
Rauen, U
机构
[1] Univ Essen Gesamthsch Klinikum, Inst Physiol Chem, D-45122 Essen, Germany
[2] Ruhr Univ Bochum, Abt Anat & Embryol, D-4630 Bochum, Germany
关键词
D O I
10.1097/01.TP.0000069830.78758.1C
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. Maintenance of the integrity of the vascular endothelium is a critical issue in liver preservation, but hypothermia, applied for cellular protection, induces apoptotic cell death in liver endothelial cells. This cold-induced apoptosis is mediated by an iron-dependent formation of reactive oxygen species. Here, we study the involvement of mitochondria in this process. Methods. Cultured rat liver endothelial cells were incubated in cold University of Wisconsin solution for 18 hr and subsequently rewarmed in cell culture medium. Mitochondrial morphology and membrane potential were evaluated using laser scanning microscopy. Results. During cold incubation in University of Wisconsin solution, a marked, progressive mitochondrial shortening and a reduction in mitochondrial membrane potential occurred. Rewarming of the cells led to mitochondrial ultracondensation, complete loss of the mitochondrial membrane potential, and subsequent apoptotic cell death. The inhibitors of mitochondrial permeability transition, trifluoperazine and fructose, or iron chelation with deferoxamine did not affect mitochondrial shortening during cold incubation but inhibited ultracondensation, loss of mitochondrial membrane potential, and loss of viability during rewarming. Moreover, in these protected cells, an almost complete reestablishment of the mitochondrial membrane potential and morphology could be observed; the few mitochondria that were irreversibly damaged were incorporated into autophagosomes during cellular recovery. Conclusion. Two apparently independent mitochondrial alterations take place during cold incubation and subsequent rewarming of liver endothelial cells. Cold-induced mitochondrial shortening represents a reversible process, whereas iron-mediated mitochondrial permeability transition and ultracondensation during rewarming are irreversible and constitute an important mediator of cold-induced apoptosis.
引用
收藏
页码:501 / 508
页数:8
相关论文
共 30 条
[1]   A subpopulation of mitochondria prevents cytosolic calcium overload in endothelial cells after cold ischemia/reperfusion [J].
Amberger, A ;
Weiss, H ;
Halter, T ;
Köck, G ;
Hermann, M ;
Widschwendter, M ;
Margreiter, R .
TRANSPLANTATION, 2001, 71 (12) :1821-1827
[2]  
Bereiter-Hahn J., 1990, International Review of Cytology, V122, P1, DOI 10.1016/S0074-7696(08)61205-X
[3]  
CALDWELLKENKEL JC, 1995, TRANSPLANT INT, V8, P77
[4]  
CARLES J, 1994, LIVER, V14, P50
[5]   Ultrastructural analysis of human endothelial cells after hypothermic storage in organ preservation solutions [J].
Eberl, T ;
Salvenmoser, W ;
Rieger, G ;
Gorny, I ;
Heiss, V ;
Kumpitsch, B ;
Gnaiger, E ;
Margreiter, R .
JOURNAL OF SURGICAL RESEARCH, 1999, 82 (02) :253-260
[6]   The mitochondrial permeability transition initiates autophagy in rat hepatocytes [J].
Elmore, SP ;
Qian, T ;
Grissom, SF ;
Lemasters, JJ .
FASEB JOURNAL, 2001, 15 (10) :2286-+
[7]   Apoptosis of sinusoidal endothelial cells is a critical mechanism of preservation injury in rat liver transplantation [J].
Gao, WS ;
Bentley, RC ;
Madden, JF ;
Clavien, PA .
HEPATOLOGY, 1998, 27 (06) :1652-1660
[9]   Morphological change, loss of Δψm and activation of caspases upon apoptosis of colorectal adenocarcinoma induced by 5-FU [J].
Ikebukuro, K ;
Adachi, Y ;
Toki, J ;
Taketani, S ;
Tokunaga, R ;
Hioki, K ;
Ikehara, S .
CANCER LETTERS, 2000, 153 (1-2) :101-108
[10]   Mitochondrial ultracondensation, but not swelling, is involved in TNF alpha-induced apoptosis in human T-lymphoblastic leukaemic cells [J].
Jia, L ;
Dourmashkin, RR ;
Newland, AC ;
Kelsey, SM .
LEUKEMIA RESEARCH, 1997, 21 (10) :973-983