Intracellular processing of apo(a) in primary baboon hepatocytes

Ann L. White, David L. Rainwater, James E. Hixson, Larry E. Estlack, Robert E. Lanford

Resultado de la investigación: Articlerevisión exhaustiva

29 Citas (Scopus)

Resumen

We have developed a serum-free medium for the long-term culture of highly differentiated primary baboon hepatocytes. Hepatocytes isolated from animals with defined plasma Lp(a) levels and apo(a) glycoprotein phenotypes were used to study the assembly of Lp(a). A combination of steady-state and pulse-chase labeling studies and endoglycosidase digests demonstrated that apo(a) was synthesized as a lower molecular weight precursor. After a prolonged period of time in the endoplasmic reticulum, apo(a) was converted to a mature form and secreted. A proportion of mature apo(a) also had a prolonged residence time in the trans Golgi apparatus. In all experiments, apoB coimmunoprecipitated with apo(a) from the culture medium but not from the cell lysates, supporting an extracellular association of the proteins for the formation of Lp(a). Analysis of hepatic RNA from 29 'null' Lp(a) phenotype baboons revealed that one-third of the animals had detectable apo(a) transcripts, whereas the remainder had no detectable apo(a) mRNA. The baboon hepatocyte system therefore represents a valuable model to examine the effect of allelic variation at the apo(a) locus on Lp(a) assembly.

Idioma originalEnglish (US)
Páginas (desde-hasta)123-133
Número de páginas11
PublicaciónChemistry and Physics of Lipids
Volumen67-68
N.ºC
DOI
EstadoPublished - ene. 1994
Publicado de forma externa

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Cell Biology

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