HDL particles containing apolipoprotein J (apoJ) have been proposed to have a regulatory function in lipid metabolism and a role in the oxidation of lipoproteins since paraxonase is present on apoJ particles. Two major subclasses of apoJ-containing particles are present in HDL including those that contain both apoJ and apoA-I (LpJ:A-I) and others that contain apoJ but not apoA-I (LpJ). To investigate the in vivo catabolism of apoJ particles, 125I-apoJ and 131I-apoA-I were reassociated with plasma lipoproteins and injected into two healthy normolipidemic volunteers. Plasma samples were separated by ultracentrifugation, FPLC and immunoaffinity chromatography. 125I-apoJ in plasma was associated with LpJ:A-I and LpJ, a lipoprotein particle slightly larger than alpha HDL analyzed by FPLC. By 2-D gel electrophoresis, the LpJ:A-I particles had alpha mobility, while the LpJ particles migrated in the pre-beta region. After ultracentrifugation, 97% of radiolabeled apoJ was located in the d>1.21g/ml in contrast to <5% of apoA-I suggesting that apoJ dissociated from the lipoprotein particles during centrifugation. During the 7 day study lipoprotein samples were fractionated by apoA-I, apoA-II and apoE immunoaffinity chromatography. The fractional catabolic rates (FCR) of plasma apolipoprotein J and A-I were 1.568+/- 0.093d-1 and 0.293+/-0.029d-1, respectively. The FCR of LpJ:A-I was much slower than LpJ (1.061+/-0.021d-1 vs 1.825+/-0.035d-1, respectively). In conclusion: 1) Plasma apoJ was catabolized 5-fold faster than apoA-I. 2) In HDL apoJ was present both on alpha migrating LpJ:A-I particles and larger pre-beta LpJ particles. 3) The catabolism of LpA-I:J was much slower than LpJ suggesting different metabolic pathways. 4) Alterations in the distribution or metabolism of apoJ are likely to have an important effect on the physiological role of apoJ in lipid metabolism and oxidation. - Human Subjects

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
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National Heart, Lung, and Blood Institute
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