Phosphatidylinositol acts through mitogen-activated protein kinase to stimulate hepatic apolipoprotein A-I secretion

An Induction in Hepatic HDL Secretion Associated with Reduced ATPase Expression

“…42 In contrast, apoA-I reuptake and degradation appears centrally important to HDL secretion and LA-phospholipid stimulants of HDL secretion appear to primarily act through this route. [25][26][27] Much as niacin, these lipids do not increase apoA-I gene transcription but instead appear to impact the secretory process by regulating the retroendocytic degradation of apoA-I (Figure 11). 26 HDL retroendocytic pathways appear to involve several cell surface HDL binding proteins.…”

“…[25][26][27] Much as niacin, these lipids do not increase apoA-I gene transcription but instead appear to impact the secretory process by regulating the retroendocytic degradation of apoA-I (Figure 11). 26 HDL retroendocytic pathways appear to involve several cell surface HDL binding proteins. A number of candidate HDL receptors have been identified in hepatocyte membranes, but the proteins shown to play the most active role in interactions with apoA-I are SR-BI and ABCA1.…”

“…However, in contrast to the fibrate drugs, LA-phospholipids do not increase cellular apoA-I mRNA levels and instead increase apoA-I secretion by blocking the endocytic recycling of apoA-I. 26 LA-phospholipids are therefore a novel class of HDL effectors that have a similar mechanism of action to niacin and are not metabolized by the cytochrome P450 enzymes. [25][26][27] Experiments were undertaken to elucidate how an LAphospholipid stimulation in apoA-I secretion may involve membrane ATPases.…”

“…26 LA-phospholipids are therefore a novel class of HDL effectors that have a similar mechanism of action to niacin and are not metabolized by the cytochrome P450 enzymes. [25][26][27] Experiments were undertaken to elucidate how an LAphospholipid stimulation in apoA-I secretion may involve membrane ATPases. We show that increased apoA-I secretion is inversely related to cell membrane ATPase protein levels.…”

“…26 LA-phospholipids appear to prevent membrane-recycling events by blocking ATPase ADP production on the cell surface and inhibiting the retroendocytic uptake of newly secreted HDL ( Figure 11). Through this mechanism, DLPC appears to act similar to other structurally dissimilar HDL raising therapeutics, which may suggest that HDL secretion is fundamentally regulated by factors that modulate the endocytic recycling of apoA-I.…”