Interspecies differences in hepatic Ca(2+)-ATPase activity and the effect of cold preservation on porcine liver Ca(2+)-ATPase function.
The accumulation of intracellular calcium ([Ca(2+)](i)) caused by ischemia-reperfusion during liver transplantation has been implicated as a factor leading to primary graft nonfunction. Plasma membrane (PM) and endoplasmic reticulum (ER) Ca(2+)-adenosinetriphosphatases (ATPases) are the primary transporters that maintain [Ca(2+)](i) homeostasis in the liver. We hypothesized that the porcine liver is better than the rat liver as a model for the study of human liver Ca(2+)-ATPase activity. We also hypothesized that cold preservation would depress Ca(2+)-ATPase activity in the porcine liver. Pig and rat livers were harvested, and human liver samples were obtained from surgical resection specimens. All were preserved with University of Wisconsin solution, and porcine livers were also preserved on ice for 2 to 18 hours. Ca(2+)-ATPase activity was measured after incubation with (45)Ca(2+) and adenosine triphosphate in the presence of specific Ca(2+)-ATPase inhibitors. Porcine PM and ER Ca(2+)-ATPase activities were 0.47 +/- 0.03 and 1.57 +/- 0.10 nmol of Ca(2+)/mg of protein/min, respectively. This was not significantly different from human liver, whereas rat liver was significantly greater at 2.60 +/- 0.03 and 9.2 +/- 0.9 nmol of Ca(2+)/mg of protein/min, respectively. We conclude that the Ca(2+)-ATPase activity in the pig liver is equivalent to that of human liver, and thus, the pig liver is a better model than the rat liver. Cold preservation studies showed a significant decrease in porcine hepatic PM Ca(2+)-ATPase activity after 4 hours of storage and near-total inhibition after 12 hours. Porcine hepatic ER Ca(2+)-ATPase activity showed a 45% decrease in activity by 12 hours and a 69% decrease by 18 hours. We conclude that cold ischemia at clinically relevant times depresses PM Ca(2+)-ATPase more than ER Ca(2+)-ATPase activity in pig liver homogenates.
Janicki
P K
PK
Department of Anesthesiology, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, 504 Oxford House, 1313 21st Ave S, Nashville, TN 37232-4125, USA. piotr.janicki@mcmail.vanderbilt.edu
Wise
P E
PE
Belous
A E
AE
Pinson
C W
CW
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000378:metabolism / Q000502:physiology*; D002462:Cell Membrane / Q000201:enzymology; D015925:Cryopreservation; D004721:Endoplasmic Reticulum / Q000201:enzymology; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013045:Species Specificity; D013552:Swine
D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases