Intracellular processing of endocytosed triglyceride-rich lipoproteins comprises both recycling and degradation

The current study was performed to investigate the intracellular fate of tr iglyceride-rich lipoproteins, Triglyceride-rich lipoproteins are responsibl e for the delivery of lipids to various tissues, however, their intracellul ar pathway has not yet been elucidated. Here radiolabeled triglyceride-rich lipoproteins, associated with lipoprotein lipase, were used for the quanti tative evaluation of the intracellular metabolism, pulse chase experiments showed that after 90 minutes approximately 60% of the labeled protein, main ly apoproteins E and C, was released intact into the medium, where it re-as sociates with lipoproteins. Apoprotein B, in contrast, was degraded, follow ing the same pathway as the apoprotein B from low density lipoproteins. In kinetic experiments uptake and intracellular fate of triglyceride-rich lipo proteins was compared to that of transferrin and low density lipoproteins. These experiments revealed that apoproteins were retained inside the cell m uch longer than transferrin, and unlike low density lipoproteins were not d egraded, Using immunofluorescence it was shown that apoprotein E and lipopr otein lipase follow a distinct route from the sorting compartment to the su rface, which is clearly distinguishable from the perinuclear transferrin re cycling compartment, In contrast, the fluorescence labeled lipids were deli vered to lysosomal compartments, The data presented here show that surface proteins of triglyceride-rich lipoproteins, such as apoproteins E and C and lipoprotein lipase follow a recycling pathway, whereas lipids and high mol ecular mass core proteins are degraded.