Effect of Nordihydroguaiaretic Acid on the Secretion of Lipoprotein Lipase

Abstract

Nordihydroguaiaretic acid (NDGA), an inhibitor of lipoxygenase, inhibits the secretion of proteins and causes the redistribution of resident Golgi proteins into the endoplasmic reticulum (ER). In this study, the effect of NDGA on lipoprotein lipase (LPL) secretion was investigated in 3T3-L1 adipocytes, and compared with those of brefeldin A (BFA), a well-known fungal metabolite that exhibits similar ER-Golgi redistribution. Both BFA and NDGA blocked secretions of LPL. In the presence of BFA, the active and dimeric LPL was accumulated in adipocytes. After endoglycosidase H (endo H) digestion, the proportion of LPL subunits with partially endo Hsensitive oligosaccharide was significantly increased with BFA. However, in the presence of NDGA, the cellular LPL became inactive, and only the endo H-sensitive fraction of the LPL subunit was observed. An increase of the aggregated forms was observed in the fractions of the sucrose-density gradient ultracentrifugation. These properties of LPL in the NDGA-treated cells were similar to those of LPL that is retained in ER, and the effects of NDGA could not be reversed by BFA. These results indicate that the inhibitory mechanism of NDGA on the LPL secretion is functionally different from the ER-Golgi redistribution that is induced by BFA.

Nordihydroguaiaretic Acid Inhibits an Activated Fibroblast Growth Factor Receptor 3 Mutant and Blocks Downstream Signaling in Multiple Myeloma Cells

“…Prior work demonstrates that strongly activated mutants of FGFR3 actually recruit JAK1 directly to the ER leading to activation of STAT family members, which is not disrupted by brefeldin A (BFA) (18, 19). In our results reported here, we found that NDGA, an agent previously shown to disrupt the Golgi by mechanisms distinct from BFA (52), rapidly blocked activation of STAT1 and STAT3. Although NDGA possesses strong antioxidant activity, the effects of NDGA on FGFR3 activation and signaling were not attributable solely to antioxidant activity, as shown by the inability of a chemically unrelated antioxidant, Zileuton, to affect FGFR3 activation.…”

Increased effect of fucoidan on lipoprotein lipase secretion in adipocytes

“…LPL plays a major role in TG metabolism and the efficiency or dysfunction of LPL has been found in association with the pathogenesis of hypertriglyceridemia (Bensadoun 1991). Previous studies have reported that a few agents increase LPL activity at transcriptional or post-transcriptional levels when added to adipocytes (Masuno and Okuda 1995;Kim et al 2002;Yang et. al.…”