Incadronate disodium inhibits advanced glycation end products-induced angiogenesis in vitro

Tamami Okamoto, Sho ichi Yamagishi, Yosuke Inagaki, Shinjiro Amano, Masayoshi Takeuchi, Seiji Kikuchi, Shigeaki Ohno, Akihiko Yoshimura

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

We have previously shown that advanced glycation end products (AGE), senescent macroprotein derivatives formed at an accelerated rate in diabetes, induced angiogenesis through overgeneration of autocrine vascular endothelial growth factor (VEGF). In the present study, effects of incadronate disodium, a nitrogen-containing bisphosphonate on AGE-elicited angiogenesis in vitro, were studied. Incadronate disodium was found to completely inhibit AGE-induced increase in DNA synthesis as well as tube formation of human microvascular endothelial cells (EC). Furthermore, incadronate disodium significantly prevented transcriptional activation of nuclear factor-κB and activator protein-1 and the subsequent up-regulation of VEGF mRNA levels in AGE-exposed EC. Farnesyl pyrophosphate, but not geranylgeranyl pyrophosphate, was found to completely restore the anti-angiogenic effects of incadronate disodium on EC. These results suggest that incadronate disodium could block the AGE-signaling pathway in microvascular EC through inhibition of protein farnesylation. Incadronate disodium may be a promising remedy for treatment of patients with proliferative diabetic retinopathy.

Original languageEnglish
Pages (from-to)419-424
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume297
Issue number2
DOIs
Publication statusPublished - 2002
Externally publishedYes

Fingerprint

Advanced Glycosylation End Products
Endothelial cells
Endothelial Cells
Vascular Endothelial Growth Factor A
Protein Prenylation
Transcription Factor AP-1
Diphosphonates
Diabetic Retinopathy
Medical problems
Transcriptional Activation
cimadronate
In Vitro Techniques
Up-Regulation
Nitrogen
Chemical activation
Derivatives
Messenger RNA
DNA
Proteins

Keywords

  • Angiogenesis
  • Diabetic retinopathy
  • Glycation
  • Incadronate disodium
  • VEGF

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Incadronate disodium inhibits advanced glycation end products-induced angiogenesis in vitro. / Okamoto, Tamami; Yamagishi, Sho ichi; Inagaki, Yosuke; Amano, Shinjiro; Takeuchi, Masayoshi; Kikuchi, Seiji; Ohno, Shigeaki; Yoshimura, Akihiko.

In: Biochemical and Biophysical Research Communications, Vol. 297, No. 2, 2002, p. 419-424.

Research output: Contribution to journalArticle

Okamoto, Tamami ; Yamagishi, Sho ichi ; Inagaki, Yosuke ; Amano, Shinjiro ; Takeuchi, Masayoshi ; Kikuchi, Seiji ; Ohno, Shigeaki ; Yoshimura, Akihiko. / Incadronate disodium inhibits advanced glycation end products-induced angiogenesis in vitro. In: Biochemical and Biophysical Research Communications. 2002 ; Vol. 297, No. 2. pp. 419-424.
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