کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2201569 | 1100026 | 2010 | 7 صفحه PDF | دانلود رایگان |
An elevated level of homocysteine (Hcy), known as hyperhomocysteinemia (HHcy), was associated with neurovascular diseases. At physiological levels, hydrogen sulfide (H2S) protected the neurovascular system. Because Hcy was also a precursor of hydrogen sulfide (H2S), we sought to test whether the H2S protected the brain during HHcy. Cystathionine-β-synthase heterozygous (CBS+/−) and wild type (WT) mice were supplemented with or without NaHS (30 μM/L, H2S donor) in drinking water. Blood flow and cerebral microvascular permeability in pial vessels were measured by intravital microscopy in WT, WT + NaHS, CBS−/+ and (CBS−/+) + NaHS-treated mice. The brain tissues were analyzed for matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) by Western blot and RT-PCR. The mRNA levels of CBS and cystathionine gamma lyase (CSE, enzyme responsible for conversion of Hcy to H2S) genes were measured by RT-PCR. The results showed a significant increase in MMP-2, MMP-9, TIMP-3 protein and mRNA in CBS (−/+) mice, while H2S treatment mitigated this increase. Interstitial localization of MMPs was also apparent through immunohistochemistry. A decrease in protein and mRNA expression of TIMP-4 was observed in CBS (−/+) mice. Microscopy data revealed increase in permeability in CBS (−/+) mice. These effects were ameliorated by H2S and suggested that physiological levels of H2S supplementation may have therapeutic potential against HHcy-induced microvascular permeability, in part, by normalizing the MMP/TIMP ratio in the brain.
Journal: Neurochemistry International - Volume 56, Issue 2, January 2010, Pages 301–307