High density lipoprotein promotes nascent apolipoprotein A-V secretion from mRNA transfected cells

Abstract

Despite its exceptionally low circulating concentration, apolipoprotein (apo) A-V is a potent modulator of plasma triacylglycerol levels. The secretion efficiency of nascent apoA-V was investigated in cultured cells transfected with mRNA. Following transfection of HepG2 cells with wild type apoA-V mRNA, apoA-V protein was detectable in cell lysates by 6 h. At 24 h post transfection, evidence of apoA-V secretion into media was obtained, although most apoA-V was recovered in the cell lysate fraction. By contrast, apoA-I was efficiently secreted into the culture medium. A positive correlation between culture medium fetal bovine serum content and the percentage of apoA-V recovered in conditioned media was observed. When transfected cells were cultured in serum-free media supplemented with increasing amounts of high density lipoprotein, a positive correlation with apoA-V secretion was observed. The data indicate that, following signal sequence cleavage, the bulk of nascent apoA-V remains cell associated. Transit of nascent apoA-V out of cultured cells is enhanced by the availability of extracellular lipid particle acceptors.

Proprotein convertase 7 (PCSK7) reduces apoA‐V levels

“…Finally, a long‐standing question relates to why apoA‐V plasma levels are exceptionally lower than those of other exchangeable apolipoproteins such as apoA1? It was hypothesized that this may be due to enhanced degradation of nascent apoA‐V protein, inefficient cotranslational translocation of apoA‐V mRNA in the ER, and its poor secretion owing to its association with cytosolic lipid droplets . Our data may shed some light on this enigma as they suggest that PC7 contributes to the observed lower levels of plasma apoA‐V.…”

“…In contrast, no changes in protein levels of plasma apoA-V were found under ND (Fig. 4D), suggesting that PC7 may specifically reduce apoA-V levels under HFD, while PC7 KO may result in higher secretion of apoA-V from the liver [26]. Our interpretation of the data is that only in the absence of PC7, there is more secretion of apoA-V from liver (less storage in cytosolic lipid droplets) thereby rationalizing the observed lower apoA-V levels therein, but higher levels in plasma.…”

Alterations in sorting and secretion of hepatic apoA5 induce hypertriglyceridemia due to short-term use of olanzapine

“…Namely, olanzapine intervention did not directly affect the transcription of apoA5. It may impair the apoA5 sorting and secretion process from hepatocytes to plasma at the post-translation level, in which the dysfunctional signal peptide of apoA5 may be involved (Romenskaia et al, 2019).…”