Hyperhomocysteinemia, a condition of elevated blood homocysteine (Hcy) level, is an independent risk factor for cardiovascular disease. Folic acid supplementation can effectively reduce blood Hcy levels. Recent studies have demonstrated that hyperhomocysteinemia is also associated with kidney disease. However, the underlying mechanisms remain unclear. The overall objective of the study was to investigate the biochemical and molecular mechanisms of Hcy-induced kidney injury and the effect of folic acid supplementation on Hcy-induced kidney injury.
Hyperhomocysteinemia was induced in Sprague-Dawley rats by feeding a high-methionine diet for 12 weeks. An elevation of serum total Hcy level was observed in hyperhomocysteinemic rats. Hyperhomocysteinemia-induced superoxide anion production via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation resulted in oxidative stress in the kidney. Reduction of oxidative stress by inhibiting superoxide anion production effectively ameliorated hyperhomocysteinemia-induced kidney injury.
Inflammatory responses such as increased chemokine expression have been implicated as one of the mechanisms of kidney disease. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that is involved in the inflammatory response in kidney disease. Nuclear factor-kappa B (NF-kappaB) plays an important role in upregulation of MCP-1 expression. We investigated the effect of hyperhomocysteinemia on MCP-1 expression and the molecular mechanism responsible for such an effect in rat kidneys as well as in human kidney proximal tubular cells.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:MWU.1993/5066 |
| Date | January 2011 |
| Creators | Hwang, Sun-Young |
| Contributors | O, Karmin (Animal Science), Guenter, Bill (Animal Science) House, Jamnes (Animal Science) Suh, Miyoung (Human Nutritional Science) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Detected Language | English |
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