The Synthesized Plant Metabolite 3,4,5-Tri-O-Galloylquinic Acid Methyl Ester Inhibits Calcium Oxalate Crystal Growth in a Drosophila Model, Downregulates Renal Cell Surface Annexin A1 Expression, and Decreases Crystal Adhesion to Cells

Mohamed Abd El-Salam, Jairo Kenupp Bastos, Jing Jing Han, Daniel Previdi, Eduardo B. Coelho, Paulo M. Donate, Michael F Romero, John C Lieske

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The plant metabolite 3,4,5-tri-O-galloylquinic acid methyl ester (TGAME, compound 6) was synthesized, and its potential effect on calcium oxalate monohydrate (COM) crystal binding to the surface of Madin-Darby canine kidney cells type I (MDCKI) and crystal growth in a Drosophila melanogaster Malpighian tubule (MT) model were investigated. Membrane, cytosolic, and total annexin A1 (AxA1), α-enolase, and heat shock protein 90 (HSP90) amounts were examined by Western blot analysis after subcellular fractionation, then confirmed by immunofluorescence staining of cultured cells. Pretreatment of MDCKI cells with TGAME for up to 6 h significantly diminished COM crystal binding in a concentration-dependent manner. TGAME significantly inhibited AxA1 surface expression by immunofluorescence microscopy, whereas intracellular AxA1 increased. Western blot analysis confirmed AxA1 expression changes in the membrane and cytosolic fractions of compound-treated cells, whereas whole cell AxA1 remained unchanged. TGAME also significantly decreased the size, number, and growth of calcium oxalate (CaOx) crystals induced in a Drosophila melanogaster MT model and possessed a potent antioxidant activity in a DPPH assay.

Original languageEnglish (US)
Pages (from-to)1609-1621
Number of pages13
JournalJournal of Medicinal Chemistry
Volume61
Issue number4
DOIs
StatePublished - Feb 22 2018

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Annexin A1
Annexins
Calcium Oxalate
Crystallization
Cell Adhesion
Drosophila
Esters
Down-Regulation
Malpighian Tubules
Kidney
Madin Darby Canine Kidney Cells
Drosophila melanogaster
Western Blotting
HSP90 Heat-Shock Proteins
Membranes
Phosphopyruvate Hydratase
Fluorescence Microscopy
Fluorescent Antibody Technique
Cultured Cells
Antioxidants

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

The Synthesized Plant Metabolite 3,4,5-Tri-O-Galloylquinic Acid Methyl Ester Inhibits Calcium Oxalate Crystal Growth in a Drosophila Model, Downregulates Renal Cell Surface Annexin A1 Expression, and Decreases Crystal Adhesion to Cells. / Abd El-Salam, Mohamed; Bastos, Jairo Kenupp; Han, Jing Jing; Previdi, Daniel; Coelho, Eduardo B.; Donate, Paulo M.; Romero, Michael F; Lieske, John C.

In: Journal of Medicinal Chemistry, Vol. 61, No. 4, 22.02.2018, p. 1609-1621.

Research output: Contribution to journalArticle

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abstract = "The plant metabolite 3,4,5-tri-O-galloylquinic acid methyl ester (TGAME, compound 6) was synthesized, and its potential effect on calcium oxalate monohydrate (COM) crystal binding to the surface of Madin-Darby canine kidney cells type I (MDCKI) and crystal growth in a Drosophila melanogaster Malpighian tubule (MT) model were investigated. Membrane, cytosolic, and total annexin A1 (AxA1), α-enolase, and heat shock protein 90 (HSP90) amounts were examined by Western blot analysis after subcellular fractionation, then confirmed by immunofluorescence staining of cultured cells. Pretreatment of MDCKI cells with TGAME for up to 6 h significantly diminished COM crystal binding in a concentration-dependent manner. TGAME significantly inhibited AxA1 surface expression by immunofluorescence microscopy, whereas intracellular AxA1 increased. Western blot analysis confirmed AxA1 expression changes in the membrane and cytosolic fractions of compound-treated cells, whereas whole cell AxA1 remained unchanged. TGAME also significantly decreased the size, number, and growth of calcium oxalate (CaOx) crystals induced in a Drosophila melanogaster MT model and possessed a potent antioxidant activity in a DPPH assay.",
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