Presence of protein-bound unconjugated bile acids in the cytoplasmic fraction of rat brain

Nariyasu Mano,Takaaki Goto,Masashi Uchida,Koji Nishimura,Masayuki Ando,Norihiro Kobayashi,Junichi Goto

doi:10.1194/jlr.m300369-jlr200

Nariyasu Mano, Takaaki Goto + Show 5 more

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https://doi.org/10.1194/jlr.m300369-jlr200

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Abstract

Using liquid chromatography/electrospray ionization mass spectrometry, we have found three unconjugated bile acids [cholic acid (CA), chenodeoxycholic acid (CDCA), and deoxycholic acid (DCA)] in the rat brain cytoplasmic fraction. CDCA was detected only upon extraction with high concentrations of guanidine, indicating that it is bound noncovalently to protein in the brain. The most abundant of the three, it was present at a concentration of 1.6 nmol/g wet weight (approximately 15 mg of protein) of brain, corresponding to almost 30 times its serum concentration. CA and DCA were present at 1/30th the concentration of CDCA. Bile acids conjugated with amino acids, sulfuric acid, and glucuronic acid were not detected. These data clearly demonstrate that unconjugated CDCA and, to a lesser extent, CA and DCA, exists in the rat brain.

Highlights

Using liquid chromatography/electrospray ionization mass spectrometry, we have found three unconjugated bile acids [cholic acid (CA), chenodeoxycholic acid (CDCA), and deoxycholic acid (DCA)] in the rat brain cytoplasmic fraction
It has been reported that 3␤-hydroxy-5-cholen-24-oic acid, whose biosynthetic pathway may pass through a 24-hydroxycholesterol intermediate, is a possible precursor for the alternative formation of chenodeoxycholic acid (CDCA) in the liver [17]
To expand upon these previous findings, the present study examines the existence of bile acids in rat brain using HPLC combined with electrospray ionization mass spectrometry (LC/ESI-MS) and an immunological method using a monoclonal antibody

Summary

Introduction

Using liquid chromatography/electrospray ionization mass spectrometry, we have found three unconjugated bile acids [cholic acid (CA), chenodeoxycholic acid (CDCA), and deoxycholic acid (DCA)] in the rat brain cytoplasmic fraction. CDCA was detected only upon extraction with high concentrations of guanidine, indicating that it is bound noncovalently to protein in the brain. Bile acids conjugated with amino acids, sulfuric acid, and glucuronic acid were not detected These data clearly demonstrate that unconjugated CDCA and, to a lesser extent, CA and DCA, exists in the rat brain.—Mano, N., T. Presence of protein-bound unconjugated bile acids in the cytoplasmic fraction of rat brain. They assist lipolysis and the absorption of fats by forming mixed micelles and return to the liver upon absorption in the ileum and proximal colon Because of their efficient hepatic uptake, bile acids have low concentrations in the peripheral blood. It was found that the organic anion-transporting polypeptide, which is known to function as an anion exchanger that facilitates the transport of anions such as bile acids from systemic portal blood into hepatocytes, is abundant in human brain [19]

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