Biosynthesis of human preproapolipoprotein A-II.

Gordon, Jeffrey I.; Budelier, Kim A.; Sims, Harold F.; Edelstein, Celina; Scanu, Angelo M.; Strauss, Arnold W.

doi:10.1016/s0021-9258(17)44023-3

Cited by 88 publications

(8 citation statements)

References 33 publications

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“…Organ cultures of fetal human and adult cynomolgus monkey intestine also failed to show apoAII synthesis (data not shown). These findings differ from previous reports suggesting that apoAII mRNA represents 0.2% of the translatable mRNA obtained from adult human jejunal epithelial cells (Gordon et al, 1983). However, we cannot rule out the possibility of active apoAII mRNA synthesis by intestinal epithelial or other intestinal cells under certain physiological conditions.…”

Section: Discussioncontrasting

confidence: 99%

“…The same conclusion was originally reached by Gordon et al (1983) poAII to apoAII conversion by a proteolytic activity secreted by HepG2 cells (Gordon et al, 1984). As discussed earlier, a significant portion of plasma apoAII results from extracellular propeptide cleavage and desialylation of the acidic apoAII isoproteins which were not accounted for in the previous studies (Gordon et al, 1983(Gordon et al, , 1984. The pulse-chase experiments with HepG2 cells indicated time-dependent depletion of the secreted higher molecular weight forms 1,-1, and -3 coupled with the concomitant accumulation of the corresponding lower molecular weight forms la, -la, and -3a.…”

Section: Discussionsupporting

confidence: 74%

“…The plasma form of human apoAII consists of two identical polypeptide chains of 77 amino acids each linked by a disulfide bond at residue 6 (Brewer et al, 1972). Protein (Gordon et al, 1983(Gordon et al, , 1984 and DNA sequence analyses of the apoAII gene (Knott et al, 1984;Lackner et al, 1984;Sharpe et al, 1984;Tsao et al, 1985) have shown that the primary translation product of apoAII mRNA consists of 100 amino acids including an 18-residue-long signal peptide (Gordon et al, 1983(Gordon et al, , 1984Knott et al, 1984;Lackner et al, 1984;Sharpe et al, 1984;Tsao et al, 1985). The newly secreted apoAII consists of 82 residues and contains a 5-residue-long N-terf Supported by grants from the National Institutes of Health (HL33952 and HL26335).…”

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confidence: 99%

“…0006-2960/90/0429-209S02.50/0 minal prosegment with the sequence AlaLeuValArgArg (Gordon et al, 1983). This prosegment is cleaved extracellularly by a thiol protease to produce the mature plasma apoAII form (Gordon et al, 1984).…”

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confidence: 99%

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Intracellular modification of human apolipoprotein AII (apoAII) and sites of apoAII mRNA synthesis: comparison of apoAII with apoCII and apoCIII isoproteins

Hussain

Zannis²

1990

Biochemistry

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We have studied the intracellular modifications of human apoAII by pulse-chase labeling of HepG2 cell cultures with [35S]methionine or [3H]arginine followed by two-dimensional analysis and autoradiography of the radiolabeled apoAII isoproteins. A short (5.0-min) pulse showed the presence of a precursor form of apoAII (pI = 5.75) designated proapoAII or apoAII3. A 5-10-min chase resulted in a decrease in the relative concentration of the proapoAII coupled with an increase in the relative concentration of a new form (pI = 5.3) designated modified proapoAII or apoAII1. Longer chase resulted in the appearance of the plasma apoAII form and at least five other acidic apoAII isoproteins in the cell lysate and the culture medium. Labeling with [3H]arginine showed that apoAII isoproteins designated 3, 1, -1, and -3 contained the prosegment whereas isoproteins designated 1a, 0, -1a, -2a, -3a, and -4a did not. Comparison of nascent apoAII, apoCII, and apoCIII isoproteins revealed that they were distinctly different on the two-dimensional gels. Neuraminidase treatment converted the acidic apoAII isoproteins to isoproteins 1a and 0 (modified and plasma apoAII forms). The combined data are consistent with the following intra- and/or extracellular modifications of apoAII: (a) modification of the apoAII which results in the net loss of two positive charges; (b) glycosylation of the modified proapoAII with carbohydrate chains containing sialic acid; (c) proteolytic removal of the prosegment and cyclization of the N-terminal glutamine. Analysis of apoAII mRNA distribution in 13 fetal human tissues as well as in cell lines of human origin showed abundance of apoAII mRNA in liver and HepG2 cells and only traces in the intestine.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 74%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Intracellular modification of human apolipoprotein AII (apoAII) and sites of apoAII mRNA synthesis: comparison of apoAII with apoCII and apoCIII isoproteins

Hussain

Zannis²

1990

Biochemistry

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“…Both the protein (Brewer et al, 1972) and the DNA sequences (Sharpe etal., 1984;Tsao etal., 1985) showed that apoA-II contains an 18-residue-long signal peptide with 0 overall charge and a 5-residue-long prosegment (Ala-Leu-Val-Arg-Arg). It has been reported that the prosegment is cleaved intraand extracellularly (Hussain et al, 1990;Gordon et al, 1983Gordon et al, , 1984) by a thiol protease displaying a cathepsin B like activity (Gordon et al, 1985). It has been shown 0006-2960/94/0433-4056S04.50/0 © 1994 American Chemical Society .3n…”

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Intracellular Early and Late Modifications of Human Apolipoprotein A-II. Effect of Glutamine-+1 to Leucine Substitution

Lopez

Roghani²,

Bertrand³

et al. 1994

Biochemistry

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It has been shown previously that apoA-II undergoes several intracellular modifications in HepG2 cells (Hussain & Zannis, 1990). In the present study, we have generated permanent cell lines in mouse C127 cells which express the normal apoA-II gene and a mutated form in which Gln+1 was substituted with Leu (Leu+1). This modification was designed to prevent cyclization of the N-terminal glutamine of apoA-II and thus identify the isoproteins which are precursors and products of the N-terminal cyclization reaction. The C127-expression cells were also utilized to study the cellular compartments where the apoA-II modifications occur as well as the importance of the modifications for apoA-II trafficking and secretion. We have found that apoA-II (Gln+1) synthesized by C127 and HepG2 cells had similar isoproteins. In both cell types, unmodified pro-apoA-II, designated isoprotein 3, had a similar isoelectric point as the cell-free translation product of apoA-II mRNA, suggesting that isoprotein 3 results from cleavage of the signal peptide. Isoprotein 3 represents an unmodified apoA-II isoprotein and undergoes an early modification into a more acidic isoprotein 1, which differs from isoprotein 3 by two negative charges. Brefeldin A treatment of the cells did not prevent the formation of isoprotein 1, suggesting that this modification occurs in a pre-Golgi compartment. Neuraminidase treatment of secreted apoA-II isoproteins did not affect isoprotein 1, indicating that it is not sialylated isoprotein. Isoprotein 1 undergoes further modifications which are consistent with cleavage of the propeptide, N-terminal cyclization and sialylation most likely resulting from O-glycosylation.(ABSTRACT TRUNCATED AT 250 WORDS)

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High‐Density Lipoproteins

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Biosynthesis of human preproapolipoprotein A-II.

Cited by 88 publications

References 33 publications

Intracellular modification of human apolipoprotein AII (apoAII) and sites of apoAII mRNA synthesis: comparison of apoAII with apoCII and apoCIII isoproteins

Intracellular modification of human apolipoprotein AII (apoAII) and sites of apoAII mRNA synthesis: comparison of apoAII with apoCII and apoCIII isoproteins

Intracellular Early and Late Modifications of Human Apolipoprotein A-II. Effect of Glutamine-+1 to Leucine Substitution

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