JOURNAL ARTICLE

Aminoguanidine inhibits advanced glycation end products formation on beta2-microglobulin

F F Hou, J Boyce, G M Chertow, J Kay, W F Owen
Journal of the American Society of Nephrology: JASN 1998, 9 (2): 277-83
9527404
Because advanced glycation end products (AGE)-modified beta2-microglobulin (AGE-beta2M) is a dominant constituent of amyloid in dialysis-related amyloidosis (DRA), AGE-beta2M may be directly involved in the pathobiology of DRA. In experimental diabetes mellitus, blocking the formation of AGE prevents AGE-mediated tissue damage. In this study, it is postulated that similar pharmacologic intervention may be beneficial in DRA. Aminoguanidine, a nucleophilic hydrazine compound that prevents AGE formation on collagen, may have a similar effect on the advanced glycation of beta2M. To test this hypothesis, beta2M was incubated in vitro with 50 or 100 mM D-glucose for 3 wk in the presence and absence of incremental concentrations of aminoguanidine. On the basis of enzyme-linked immunosorbent assay and immunoblots using anti-AGE-keyhole limpet hemocyanin antibody, aminoguanidine inhibited glucose-induced N(epsilon)-(carboxymethyl)lysine formation on beta2M. At aminoguanidine-glucose molar ratios of 1:8 to 1:1, 26 to 53% inhibition occurred. Fluorospectrometry examination showed that aminoguanidine also inhibited the formation of fluorescent AGE on beta2M in a dose-dependent manner. At aminoguanidine-glucose molar ratios of 1:8 to 1:1, fluorescent product generation was inhibited by 30 to 70%. Furthermore, aminoguanidine suppressed the AGE formation on beta2M bound to AGE-modified collagen. If aminoguanidine is similarly active in vivo, this compound may be of clinical utility for treating DRA in patients on maintenance dialysis.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Remove bar
Read by QxMD icon Read
9527404
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"