Plasma and hepatic apoE isoproteins of nonhuman primates. Differences in apoE among humans, apes, and New and Old World monkeys.

V I Zannis,R J Nicolosi,E Jensen,J L Breslow,K C Hayes

doi:10.1016/s0022-2275(20)34247-4

Abstract

We have used two-dimensional polyacrylamide gel electrophoresis (PAGE) to study the plasma and hepatic apoE isoproteins of nonhuman primates and have compared them with their human counterparts. We have found that apoE obtained from fresh monkey or ape plasma, as well as nascent apoE synthesized by perfused monkey livers, is composed of several isoproteins that resemble the homozygous (beta) apoE phenotype observed in humans. The nonhuman primate plasma apoE pattern of 90 animals from nine different species consisted of a major isoprotein designated apoE3 and a few minor isoproteins. A group of acidic apoE isoproteins is eliminated after treatment with C. perfringens neuraminidase and has been designated sialo apoE (apoEs). Nonhuman primate liver apoE isoproteins comigrate with their plasma apoE isoprotein counterparts on two-dimensional PAGE, but hepatic apoE is enriched in sialo apoE isoproteins when compared to plasma apoE. The apparent molecular weight of asialo and sialo apoE obtained from Old World monkeys and apes is identical to the molecular weight of the corresponding human isoproteins (E3 = 38K, Es = 38.5-39.5K). However, the apparent molecular weight of apoE isoproteins obtained from New World monkeys is increased by approximately 0.5K (E3 = 38.5K, Es = 39.0-40.0K) as compared to the molecular weight of human and Old World monkey and ape isoproteins. The isoelectric points of apoE3 obtained from Old World monkeys, New World monkeys, chimpanzees, and gibbons are 5.74, 5.76, 5.95, and 5.89, respectively. The entire New or Old World monkey, chimpanzee, and gibbon apoE pattern is shifted by approximately -2.0, -0.5, and -1.0 charges, respectively, relative to the pattern of the corresponding human E3/3 phenotype. The molecular weight difference in apoE observed among New and Old World monkeys, as well as the molecular weight and/or charge differences observed among monkey, ape, and human apoE are consistent with structural changes in the apoE gene which have occurred following the divergence of the different species. The observation of only the homozygous apoE phenotypes in all animals studied suggests that the common apoE genetic polymorphism recently described in humans may not be present in nonhuman primates.

Highlights

IntroductionThe entire New or Old World monkey, chimpanzee, and gibbon apoE pattern is shifted by approximately -2.0,-0.5, and -1.0 charges, respectively, relative to the pattern of the corresponding human E3/3 phenotype
Sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis of plasma lipoproteins separated by density gradient ultracentrifugation
Numerous studies have established that apoE plays an important role in lipoprotein catabolism by extrahepatic tissues [17,18,19]

Summary

Introduction

The entire New or Old World monkey, chimpanzee, and gibbon apoE pattern is shifted by approximately -2.0,-0.5, and -1.0 charges, respectively, relative to the pattern of the corresponding human E3/3 phenotype. The observation of only the homozygous apoE phenotypes in all animals studied suggests that the common apoE genetic polymorphism recently. We have recently reported an extensive polymorphism of apoE in humans which results in part from genetic variability of the apoE allele in the humanpopulation and from a post-translational modification of an original apoE polypeptide with carbohydrate chains containing sialic acid [28,29,30,31]. The purpose of the present study was to investigate the biochemical characteristics of plasma and hepatic apoE in nonhuman primates and search for inter- and intra-species variability in apoE

Objectives

Results

Conclusion