Interaction of Native- and Oxidized-Low-Density Lipoprotein with Human Estrogen Sulfotransferase.

Abstract

Cytosolic estrogen sulfotransferase (SULT1E) mainly catalyzes the sulfate conjugation of estrogens, which decrease atherosclerosis progression. Recently we reported that a YKEG sequence in human SULT1E1 (hSULT1E1) corresponding to residues 61-64 can bind specifically to oxidized low-density lipoprotein (Ox-LDL), which plays a major role in the pathogenesis of atherosclerosis; its major oxidative lipid component lysophosphatidylcholine (LPC), and its structurally similar lipid, platelet-activating factor (PAF). In this study, we investigated the effect of Ox-LDL on the sulfating activity of hSULT1E1. In vivo experiments using a mouse model of atherosclerosis showed that the protein expression of SULT1E1 was higher in the aorta of mice with atherosclerosis compared with that in control animals. Results from a sulfating activity assay of hSULT1E1 using 1-hydroxypyrene as the substrate demonstrated that Ox-LDL, LPC, and PAF markedly decreased the sulfating activity of hSULT1E1, whereas native LDL and 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC) as one of the oxidized phosphatidylcholines showed the opposite effect. The sulfating activity greatly changed in the presence of LPC, PAF, and POVPC in their concentration-dependen manner (especially above their critical micelle concentrations). Moreover, Ox-LDL specifically recognized dimeric hSULT1E1. These results suggest that the effects of Ox-LDL and native LDL on the sulfating activity of hSULT1E1 might be helpful in elucidating the novel mechanism underlying the pathogenesis of atherosclerosis, involving the relationship between estrogen metabolism, LDL, and Ox-LDL.

• Authors: Akira Sato, Hinako Watanabe, Miyuki Yamazaki, Eiko Sakurai, Keiichi Ebina
• Journal: The protein journal (Protein J) Vol. 40 Issue 2 Pg. 192-204 (04 2021) ISSN: 1875-8355 [Electronic] Netherlands
• PMID: 33665770 (Publication Type: Journal Article)

Chemical References

• Lipoproteins, LDL
• Lysophosphatidylcholines
• Platelet Activating Factor
• oxidized low density lipoprotein
• Sulfotransferases
• estrone sulfotransferase

Topics

• Animals
• Atherosclerosis
• Humans
• Lipoproteins, LDL (chemistry, metabolism)
• Lysophosphatidylcholines (metabolism)
• Male
• Mice
• Mice, Knockout
• Platelet Activating Factor (metabolism)
• Protein Binding
• Sulfotransferases (chemistry, metabolism)