Homocysteine stimulates monocyte chemoattractant protein-1 expression in the kidney via nuclear factor-κB activation

Sun Young Hwang, Connie W.H. Woo, Kathy K W AU YEUNG, Yaw L. Siow, Tong Y. Zhu, Karmin O*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

Hyperhomocysteinemia, or an elevation of blood homocysteine (Hcy) levels, is associated with cardiovascular disorders. Although kidney dysfunction is an important risk factor causing hyperhomocysteinemia, the direct effect of Hcy on the kidney is not well documented. There is a positive association between an elevation of blood Hcy levels and the development of chronic kidney disease. Inflammatory response such as increased chemokine expression has been implicated as one of the mechanisms for renal disease. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that is involved in the inflammatory response in renal disease. Nuclear factor-κB (NF-κB) plays an important role in upregulation of MCP-1 expression. We investigated the effect of hyperhomocysteinemia on MCP-1 expression and the molecular mechanism underling such an effect in rat kidneys as well as in proximal tubular cells. Hyperhomocysteinemia was induced in rats fed a high-methionine diet for 12 wk. The MCP-1 mRNA expression and MCP-1 protein levels were significantly increased in kidneys isolated from hyperhomocysteinemic rats. The NF-κB activity was significantly increased in the same kidneys. Pretreatment of hyperhomocysteinemic rats with a NF-κB inhibitor abolished hyperhomocysteinemia-induced MCP-1 expression in the kidney. To confirm the causative role of NF-κB activation in MCP-1 expression, human kidney proximal tubular cells were transfected with decoy NF-κB oligodeoxynucleotide to inhibit NF-κB activation. Such a treatment prevented Hcy-induced MCP-1 mRNA expression in tubular cells. Our results suggest that hyperhomocysteinemia stimulates MCP-1 expression in the kidney via NF-κB activation. Such an inflammatory response may contribute to renal injury associated with hyperhomocysteinemia.

Original languageEnglish
Pages (from-to)F236-F244
JournalAmerican Journal of Physiology - Renal Physiology
Volume294
Issue number1
DOIs
Publication statusPublished - Jan 2008

Scopus Subject Areas

  • Physiology
  • Urology

User-Defined Keywords

  • Hyperhomocysteinemia

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