Bile acids in tissues: Binding of lithocholic acid to protein

Nair, Padmanabhan P.; Solomon, Robert D.; Bankoski, Joyce; Plapinger, Robert E.

doi:10.1007/bf02533857

Cited by 27 publications

(9 citation statements)

References 17 publications

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“…Low doses of primary bile acids increase the number of aberrant crypt foci in the colon (29); conversely, higher concentrations of deoxycholic acid induce apoptosis in colon cancer cells (30). Nair et al (31) have found a tissue-bound form of lithocholate with a free form in human liver, which can be hydrolytically released using clostridial cholanoylamino acid hydrolase. They have demonstrated a specific conjugation of the ⑀-amino group of a lysine residue to the carboxyl group of a bile acid and investigated the relationship to promotion of carcinogenesis (32).…”

Section: Discussionmentioning

confidence: 99%

A Nonenzymatic Modification of the Amino-terminal Domain of Histone H3 by Bile Acid Acyl Adenylate

Mano

Kasuga

Kobayashi

et al. 2004

Journal of Biological Chemistry

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Although it has been proposed that the secondary bile acids, deoxycholic acid and lithocholic acid, increase the number of aberrant crypt foci in the colon and may act as colon tumor promoters, there is little evidence detailing their mechanism of action. Histones play an important role in controlling gene expression, and the posttranslational modification of histones plays a role in regulation of intracellular signal transduction. In particular, the amino-terminal tail domain of histone H3 is sensitive to several posttranslational modifications, and acetylation of this domain changes its electrostatic environment and results in the loss of native folding. Therefore, we studied the modification of ⑀-amino groups on human histone H3 by deoxycholyl adenylate, which is an active intermediate in deoxycholyl thioester biosynthesis. After incubation of recombinant human histone H3 with a smaller amount of acyl adenylate, followed by enzymatic digestion, the peptide fragment mixtures were analyzed by matrix-assisted laser desorption ionization mass spectrometry. These data showed the formation of only one adduct fragment, which corresponded to amino acids 3-8 with a deoxycholate adduct, suggesting that the ⑀-amino group of Lys 4 had the highest reactivity. This novel modification, formation of a bile acid adduct on the histone H3 amino-terminal tail domain through an active acyl adenylate, may relate to the carcinogenesis-promoting effects of secondary bile acids.

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Section: Discussionmentioning

confidence: 99%

A Nonenzymatic Modification of the Amino-terminal Domain of Histone H3 by Bile Acid Acyl Adenylate

Mano

Kasuga

Kobayashi

et al. 2004

Journal of Biological Chemistry

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“…While they each display an [M -57]+ ion, the ion relative abundances vary and, unlike the carboxylic acid substituents, it is not the dominant ion in the high-mass region of their spectra. N-( 1-Propy1)lithocholylamide (4) has the most pronounced [M -57]+ ( Fig. 7(a), m/z 360).…”

Section: Effect Of Other N-substituents On the Mass Spectra Of Lithocmentioning

confidence: 99%

Electron impact ionization mass spectra of lithocholyl amides: Evidence for a C(20) to C(23) rearrangement involving the loss of a C₄H₉ fragment

Nair

Flanagan

Oliver

1994

Org. Mass Spectrom.

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Amides of lithocholic acid (3a-hydroxy-5~-cholan-24-oic acid) with daminocaproic acid and Caminobutyric acid were prepared and examined by electron impact ionization mass spectrometry. Both these compounds gave an unusual [ M -57 1 + fragment. Since the product-ion analysis of [ M -57 1 + revealed the presence of fragments corresponding to the intact steroid nucleus in addition to that of the original amino acid (daminocaproic acid or Caminobutyric acid), we concluded that the integrity of the steroid amide had been retained in this fragment. The absence of this fragment from the product-ion spectrum of [M -CH3]+ rules out the sequential loss from the molecular ion of 15 + 42 u as the origin of this signal. Mass spectrometry of the 2d13C-labeUed lithe cholylcaproylamide showed the retention of the label in the [ M -571 + fragment. In contrast, the corresponding compound labelled with deuterium at C(23) showed a significant loss of the label during the formation of this product ion at [ M -581 +. In addition, through a combination of derivatization and tandem mass spectrometry, it was demonstrated that this loss of 57 u represented a rearrangement with the expulsion of a C,H, radical from the side-chain spanning C(20) to C(23) resulting in a truncated steroid-amide fragment. This fragmentation pattern has not been observed in bile acid conjugates with N-a-amino acids.

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“…In 1977, lithocholic acid (LCA), a hydrophobic bile acid, was firstly isolated as a tissue-bound form from pathological specimens of human livers by Nair et al, 1,2 and its concentration was reported to be elevated in the livers of rat treated with a carcinogen, methylazoxymethanol. 3 Furthermore, the tissuebound LCA was detected in normal and neoplastic human mammary tissues and in the neoplasms of the uterus, kidney, lung and the colon.…”

Section: Introductionmentioning

confidence: 99%

Production and Characterization of a Monoclonal Antibody to Capture Proteins Tagged with Lithocholic Acid

et al. 2008

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Reactive metabolic-modified proteins have been proposed to play an important role in the mechanism(s) of the hepatotoxicity and colon cancer of lithocholic acid (LCA). To identify cellular proteins chemically modified with LCA, we have generated a monoclonal antibody that recognizes the 3a-hydroxy-5b-steroid moiety of LCA. The spleen cells from a BALB/c mouse, which was immunized with an immunogen in which the side chain of LCA was coupled to bovine serum albumin (BSA) via a succinic acid spacer, was fused with SP2/0 myeloma cells to generate antibody-secreting hybridoma clones. The resulting monoclonal antibody (g2b, k) was specific to LCA-N a -BOC-lysine as well as the amidated and nonamidated forms of LCA. The immunoblot enabled the detection of LCA residues anchored on BSA and lysozyme. The antibody will be useful for monitoring the generation, localization, and capture of proteins tagged with LCA, which may be the cause of LCA-induced toxicity.

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Bile acids in tissues: Binding of lithocholic acid to protein

Cited by 27 publications

References 17 publications

A Nonenzymatic Modification of the Amino-terminal Domain of Histone H3 by Bile Acid Acyl Adenylate

A Nonenzymatic Modification of the Amino-terminal Domain of Histone H3 by Bile Acid Acyl Adenylate

Electron impact ionization mass spectra of lithocholyl amides: Evidence for a C(20) to C(23) rearrangement involving the loss of a C₄H₉ fragment

Production and Characterization of a Monoclonal Antibody to Capture Proteins Tagged with Lithocholic Acid

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Bile acids in tissues: Binding of lithocholic acid to protein

Cited by 27 publications

References 17 publications

A Nonenzymatic Modification of the Amino-terminal Domain of Histone H3 by Bile Acid Acyl Adenylate

A Nonenzymatic Modification of the Amino-terminal Domain of Histone H3 by Bile Acid Acyl Adenylate

Electron impact ionization mass spectra of lithocholyl amides: Evidence for a C(20) to C(23) rearrangement involving the loss of a C4H9 fragment

Production and Characterization of a Monoclonal Antibody to Capture Proteins Tagged with Lithocholic Acid

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Electron impact ionization mass spectra of lithocholyl amides: Evidence for a C(20) to C(23) rearrangement involving the loss of a C₄H₉ fragment