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

Abstract

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.

Improved vessel preservation after 4 days of cold storage: Experimental study in rat arteries

“…Similarly, the endothelial cell injury in cold-stored porcine aorta was inhibited by the iron chelators deferoxamine and LK 614, 18 and in the present study the protective effect of solution 8 is augmented by the presence of the same iron chelators. This confirms in vitro data (cultured endothelial cells) that chelatable iron is an important factor causally involved in cold-induced endothelial injury 11,[27][28][29] and adds further evidence that this concept is valid for clinically-relevant storage conditions. Protective principles of the new vascular preservation solution.…”

Cold-induced injury to lung epithelial cells can be inhibited by iron chelators — implications for lung preservation☆

“…The increase in cellular chelatable iron ions has been described to occur rapidly after initiation of cold incubation in hepatocytes and on a somewhat longer timescale in renal tubular cells. If oxygen is present, this increased availability of redox-active iron ions leads to marked lipid peroxidation and to a mitochondrial permeability transition or mitochondrial ultracondensation, both mitochondrial alterations known to be involved in apoptotic pathways, and both being inhibited by the use of iron chelators [5,10,11].…”

Invited speaker’s papers and abstracts

“…Cytochrome P-450 activity requires the availability of free NADPH in the cytosol, which is generated both in the oxidative stage of the pentose phosphate pathway and in the pyruvate-malate cycle by functional mitochondria (Mandl et al, 1995). Cryopreservation has been reported to perturb mitochondrial function in cryopreserved (Dabos et al, 2002;Lawrence and Benford, 1991) and hypothermically stored (Kerkweg et al, 2003) hepatocytes, but to our knowledge this has not been investigated in rat hepatocytes cryopreserved as monolayers. In the present study, the mitochondrial membrane potential ( Ψ mit ) of primary rat hepatocytes cultured and cryopreserved as monolayers of cells on collagen coated culture dishes was assessed by the fluorescent Ψ mit indicator tetramethylrhodamine ethyl ester (TMRE).…”

“…Petri dishes (60 mm) coated with 30 g/cm 2 type I collagen isolated from rat tail tendons were seeded with 3 × 10 6 viable cells in 2 ml Chee's medium containing 5% (v/v) foetal calf serum (FCS). Monolayer 24 h cultures of hepatocytes were frozen for 24 h at −70 • C in 10% dimethyl sulfoxide and 90% foetal calf serum (Watts and Grant, 1996). Ψ mit was measured by incubation with 100 nM TMRE for 20 min at room temperature and imaging under a confocal laser scanning microscope.…”