Hereditary and dietary effects on apolipoprotein[a] isoforms and Lp[a] in baboons.

Rainwater, David L.; Manis, Georgios; VandeBerg, John L.

doi:10.1016/s0022-2275(20)38340-1

Cited by 68 publications

(3 citation statements)

References 25 publications

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“…Baboons show characteristics similar to humans in terms of their plasma Lp[a] levels and apo[a] isform sizes (26,27). We have established primary baboon hepatocyte cultures as a model system to study Lp[a] biogenesis (6 -8, 23, 28, 29).…”

Section: Lipoprotein [A] (Lp[a]mentioning

confidence: 99%

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Presecretory degradation of apolipoprotein[a] is mediated by the proteasome pathway

White

Guerra

Wang

et al. 1999

Journal of Lipid Research

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Plasma levels of atherogenic lipoprotein [a] (Lp[a]) vary over a 1000-fold range and are largely determined by the gene for its unique glycoprotein, apolipoprotein [a] (apo[a]). The apo[a] locus comprises more than 100 alleles, encoding proteins from Ͻ 300 to Ͼ 800 kDa. Using primary baboon hepatocyte cultures, we previously demonstrated that differences in the secretion efficiency of apo[a] allelic variants contribute to the variation in plasma Lp[a] levels. In the current study, we investigated the mechanism of apo[a] presecretory degradation. The proteasome inhibitors, acetyl-leucyl-leucyl-norleucinal and lactacystin, prevented apo[a] degradation and increased apo[a] secretion. Transfection with an HA-tagged ubiquitin construct demonstrated the accumulation of ubiquitinated apo[a] in the presence of lactacystin. These results suggest a role for the cytoplasmic proteasome in apo[a] proteolysis. Apo[a] that accumulated intracellularly in the presence of lactacystin remained sensitive to endo-B-N-glucosaminidase H, and apo[a] degradation was reversibly inhibited by brefeldin A, suggesting that transport to a post-endoplasmic reticulum (ER) pre-medial Golgi compartment is required for apo[a] degradation. Newly synthesized apo[a] bound to the ER chaperone calnexin and conditions that enhanced this interaction prevented apo[a] degradation, suggesting that calnexin can protect apo[a] from proteolysis. These studies provide further support for the role of the proteasome in endoplasmic reticulum quality control, and expand this role to one that influences plasma levels of the atherogenic lipoprotein Lp[a].-White, A. L., B. Guerra, J. Wang, and R. E. Lanford. Presecretory degradation of apolipoprotein[a] is mediated by the proteasome pathway.

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Section: Lipoprotein [A] (Lp[a]mentioning

confidence: 99%

“…Hepatocytes from two different animals were analyzed. Apo[a] isoforms in the baboon are classified into 12 size groups; A, the largest, through L, the smallest (27). One animal expressed an A isoform and had a plasma Lp[a] level of 17 mg/dL.…”

Section: Hepatocyte Isolation and Culturementioning

confidence: 99%

Presecretory degradation of apolipoprotein[a] is mediated by the proteasome pathway

White

Guerra

Wang

et al. 1999

Journal of Lipid Research

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“…Diet 130–133 and cholesterol‐lowering drugs, with the exception of niacin, appear to have little effect on Lp(a) levels 47 , 134–138 . Neomycin 135 and fish oil 139 have been shown to lower Lp(a) concentrations, and norethisterone has also been shown to reduce Lp(a) levels in postmenopausal women, 140 although the mechanism of action in all cases is unknown.…”

Section: Treatment Of Elevated Lp(α) Levelsmentioning

confidence: 99%

LIPOPROTEIN(α) IN HEALTH AND DISEASE

Byrne

Wild

1994

Int J Clinical Practice

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SUMMARY Elevated plasma levels of Lp(a) do seem to influence the progression of atherosclerosis. Evidence is emerging that certain apo(a) isoforms may be more atherogenic than others, and in transgenic mice free apo(a) has been shown to be associated with accelerated atherosclerosis. Currently it is not known whether treating elevated Lp(a) levels will reduce progression of atherosclerosis and, as therapeutic options are limited, mass screening of Lp(a) levels in populations is not indicated. The presence of raised Lp(a) levels, however, warrants aggressive treatment to reduce other cardiovascular risk factors. Continuing research to investigate the relationship of the apo(a) gene to other genes, including the plasminogen gene and apo(a)‐related genes, will add further information pertaining to the evolution, function, regulation and clinical implications of Lp(a).

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Pipoprotein Lp(a): Effects of allelic variation at theLPA locus

Rainwater¹,

Kammerer²

1998

J. Exp. Zool.

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Hereditary and dietary effects on apolipoprotein[a] isoforms and Lp[a] in baboons.

Cited by 68 publications

References 25 publications

Presecretory degradation of apolipoprotein[a] is mediated by the proteasome pathway

Presecretory degradation of apolipoprotein[a] is mediated by the proteasome pathway

LIPOPROTEIN(α) IN HEALTH AND DISEASE

Pipoprotein Lp(a): Effects of allelic variation at theLPA locus

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