Sunday, 8 June 2014

Homocysteine, gut permeability and MMP-9?

A speculative post this one, on the paper by Hao Ding and colleagues [1] (open-access here) looking at how, in a rodent model of colitis, homocysteine (the big 'H') might play some part in aggravating "inflammatory damage" potentially through promotion of some of the matrix metalloproteinases, MMP-2 and MMP-9. The words: "Hcy [homocysteine] can increase intestinal permeability" added to the interest.

If you're used to reading about autism research on this blog, you might be wondering why on earth I've posted about this study. Well, with that pinch of salt at the ready, the Ding study got some of the grey-pinkish matter thinking...


OK, I know there's been speculation a-plenty in this post and by saying all of this I am by no means try to pin everything on homocysteine, MMP-9 or anything else when it comes to autism. I would never be that silly. I would however suggest that there is a study or two to be done based on these speculations, asking questions about whether MMP-9 is truly elevated in some cases of autism, and whether homocysteine levels or gut permeability measures may show some connection to one and another and MMP-9. That also the Ding paper focused on an animal model of acquired colitis, an inflammatory bowel disease, also offers another potential differentiating factor if one is to assume that autism is not protective of any other condition, including those of the inflammatory bowel disease grouping (see here and see here). I could go on further and bring GABA receptors and how use of something like "The GABA-A receptor agonist, muscimol ameliorated the Hcy-mediated MMP-9 activation" [7] (open-access here) but that's perhaps another topic for another day, alongside minocycline [8] or even melatonin [9]. 

I'm quite finished now. Apart, that is, from telling you that You Give Love a Bad Name... (the Bon Jovi song that is, not necessarily you personally).

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[1] Ding H. et al. Effect of homocysteine on intestinal permeability in rats with experimental colitis, and its mechanism. Gastroenterol Rep (Oxf). 2014 Apr 27.

[2] Kałużna-Czaplińska J. et al.  A focus on homocysteine in autism. Acta Biochim Pol. 2013;60(2):137-42.

[3] Tu WJ. et al. Serum homocysteine concentrations in Chinese children with autism. Clin Chem Lab Med. 2013 Feb;51(2):e19-22.

[4] Lee SJ. et al. Homocysteine enhances MMP-9 production in murine macrophages via ERK and Akt signaling pathways. Toxicol Appl Pharmacol. 2012 Apr 1;260(1):89-94.

[5] Abdallah MW. et al. Amniotic fluid MMP-9 and neurotrophins in autism spectrum disorders: an exploratory study. Autism Res. 2012 Dec;5(6):428-33. 

[6] Munjal C. et al. Matrix metalloproteinase-9 in homocysteine-induced intestinal microvascular endothelial paracellular and transcellular permeability. J Cell Biochem. 2012 Apr;113(4):1159-69.

[7] Tyagi N. et al. Activation of GABA-A receptor ameliorates homocysteine-induced MMP-9 activation by ERK pathway. J Cell Physiol. 2009 Jul;220(1):257-66. 

[8] Dziembowska M. et al. High MMP-9 activity levels in fragile X syndrome are lowered by minocycline. Am J Med Genet A. 2013 Aug;161A(8):1897-903. 

[9] Rudra DS. et al. Melatonin inhibits matrix metalloproteinase-9 activity by binding to its active site. J Pineal Res. 2013 May;54(4):398-405. 

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ResearchBlogging.org Ding H, Mei Q, Gan HZ, Cao LY, Liu XC, & Xu JM (2014). Effect of homocysteine on intestinal permeability in rats with experimental colitis, and its mechanism. Gastroenterology report PMID: 24787389