Expression of apolipoprotein[a] and plasminogen mRNAs in cynomolgus monkey liver and extrahepatic tissues

R Ramharack,M A Spahr,J S Kreick,C S Sekerke

doi:10.1016/s0022-2275(20)37567-2

Abstract

The apolipoprotein[a] (apo[a]) and plasminogen (PLG) genes share a high degree of sequence identity, suggesting that both genes may be coordinately expressed. To address this possibility, hepatic apo[a], PLG, and glyceraldehyde-3-phosphate dehydrogenase (G3PDH) mRNAs in 11 cynomolgus monkeys that express plasma Lp[a] over a 10-fold range (5.3-69.3 mg/dl) were measured. This analysis demonstrated a 13-fold variation in apo[a] mRNA. PLG mRNA levels ranged only 3-fold, which was similar to the deviation in G3PDH mRNA expression. Lp[a] and PLG plasma levels were also not related in the animals. To further define expression of the latter mRNAs, they were measured in liver and 13 extrahepatic tissues from 5 monkeys. Apo[a] transcript was detected for the first time in adrenal, lung, and pituitary in addition to brain and testes. PLG mRNA was detected extrahepatically only in testes while G3PDH mRNA was ubiquitously expressed. In individual animals, there was no relationship between hepatic and extrahepatic apo[a] mRNA levels suggesting tissue-dependent expression of the transcript. These results demonstrate that although the apo[a] and PLG genes are highly homologous, their mRNA expression differs markedly.

Highlights

IntroductionThere was no relationship between hepatic and extrahepatic apo[a]
The liver is the major site of both apo[a] and PLG mRNA synthesis[32,33], we decided to examine the relationship between hepatic apo[a] and PLG mRNA levels
Monkey apo[a] mRNA levels in these experiments were determined by a specific ribonuclease protection assay that uses a kringle IV type-1 probe as previously characterized [34]

Summary

Introduction

There was no relationship between hepatic and extrahepatic apo[a] These results demonstrate that the apo[a] and PLG genes are highly homologous, their mRNA expression differs markedly.-Ramharack, R., M. The apo[a] 5'- and 3'-untranslated regions are 98% and 87% homologous, respectively, to the corresponding sequences in plasminogen mRNA [24].There are four protein coding domains in apofa] that share extensive identity (78- 100%)with plasminogen. The kringle IV sequence is repeated from 12 to >40 times in apo[a] which distinguishes it from other kringle IV-containing sequences including several apo[a]-related genes (apo[a]-rg)(26).Analysis of an apo[a] cDNA containing 37 kringle IV sequences [24] showed that there are 10 different kringle IV subtypes, designated as types 1-10, that are 78438% identical to PLG kringle IV at the protein level. 3-10 kringle IV sequences are present as single copies in apo[a] whereas kringle IV, type-2, is the major identically repeated kringle [27] and is responsible for the protein isoform size differences in apo[a] that range from 300 to ,800 kDa [28, 29]

Methods

Results

Conclusion