Effect of Carnosine and Related Compounds on the Inactivation of Human Cu,Zn-Superoxide Dismutase by Modification of Fructose and Glycolaldehyde

Abstract

Glycolaldehyde, an intermediate of the Maillard reaction, and fructose, which is mainly derived from the polyol pathway, rapidly inactivate human Cu,Zn-superoxide dismutase (SOD) at the physiological concentration. We employed this inactivation with these carbonyl compounds as a model glycation reaction to investigate whether carnosine and its related compounds could protect the enzyme from inactivation. Of eight derivatives examined, histidine, Gly-His, carnosine and Ala-His inhibited the inactivation of the enzyme by fructose (p<0.001), and Gly-His, Ala-His, anserine, carnosine, and homocarnosine exhibited a marked protective effect against the inactivation by glycolaldehyde (p<0.001). The carnosine-related compounds that showed this highly protective effect against the inactivation by glycolaldehyde had high reactivity with glycolaldehyde and high scavenging activity toward the hydroxyl radical as common properties. On the other hand, the carnosine-related compounds that had a protective effect against the inactivation by fructose showed significant hydroxyl radical-scavenging ability. These results indicate that carnosine and such related compounds as Gly-His and Ala-His are effective anti-glycating agents for human Cu,Zn-SOD and that the effectiveness is based not only on high reactivity with carbonyl compounds but also on hydroxyl radical scavenging activity.

Biological activities of the natural imidazole-containing peptidomimetics n-acetylcarnosine, carcinine and l-carnosine in ophthalmic and skin care products

“…The protective effect of the carnosine-related compounds against the inactivation of Cu,Zn-SOD and ceruloplasmin in conditions of oxidative stress and glycation was described in the recent in vitro experiments (Ukeda et al, 2002;Kang et al, 2002a,b,c). In one of these studies (Kang et al, 2002a) the protective effects of carnosine and related compounds against the oxidative damage of human Cu,Zn-superoxide dismutase (SOD) by peroxyl radicals generated from 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) were examined.…”

Effect of histidine on autotaxin activity in experimentally induced liver fibrosis

“…These findings indicated that histidine may aid in an enzymatic reaction and possessed antioxidant activities, which definitely contributed to the hepatic antioxidant protection. Also, it could exhibit antioxidant activities via nonenzymatic actions such as scavenging free radicals and binding divalent metal ions [11].…”

“…Studies have demonstrated the beneficial effect of antioxidants in protecting the liver against TAAinduced injury [10][11][12].…”

“…Histidine, in addition to a routine metabolic role as a protein-building block, is an effective scavenger of toxic oxygen species by direct interactions of the histidine imidazole ring with a singlet oxygen or by interfering with the redox reactions, involving metal ions that produce the hydroxyl radical [11]. Therefore, it is useful in protecting cells and tissues from a variety of inflammatory disease processes [12].…”

Amino acids exhibit anti-inflammatory effects in human monocytic leukemia cell line, THP-1 cells

“…levels through activation of the glycine-gated chloride channels [26,27,41]. In addition, glycine also exhibits inhibitory effects in alveolar macrophages or T cells in vitro [25,26], and some reports have shown that histidine also exhibits antioxidant effects such as scavenging free radicals, binding divalent metal ions and glycating actions [42][43][44]. Previous reports have suggested that histidine inhibit NFjB activation and IL-8 production in intestinal epithelial cells stimulated with TNF-a or lipopolysaccharide (LPS) [23], and that histidine also inhibits NF-jB activation and cytokine production in LPS-stimulated murine peritoneal macrophages in vitro [29].…”