Glycoxidation and lipid peroxidation of low-density lipoprotein can synergistically enhance atherogenesis.

OBJECTIVE: The purpose of this study was to clarify the role of glycoxidation and lipid peroxidation of low-density lipoprotein (LDL) in atherogenesis. METHODS AND RESULTS: We examined the formation of N(epsilon)-(carboxymethyl) lysine (CML), a glycoxidation product, and malondialdehyde (MDA), a lipid peroxidation product, in vitro and their co-localization in human atherosclerotic lesions. Immunochemical analysis revealed that CML was formed in a time-dependent manner by human LDL incubated with copper ions and glucose, i.e. an in vitro model of glycoxidation of LDL. When LDL was exposed to copper ions alone, a small amount of CML was formed, however this was significantly less in oxidized LDL than glycoxidative LDL. In contrast, MDA formation was observed in both oxidation and glycoxidation of LDL, but not in glycation of LDL. Hexitol-lysine (HL), an Amadori product, was formed by both glycation and glycoxidation of LDL, but not by oxidation of LDL. Immunohistochemical analysis showed that CML and MDA accumulated mainly in macrophage/foam cells, while pyrraline, a non-oxidative product of glycation, and apolipoprotein B were localized in the extracellular matrix in atherosclerotic lesions. Atheromas were positive for CML and MDA, but negative for pyrraline. Macrophage/foam cells in atherosclerotic lesions exhibited co-localization of macrophage scavenger receptor-A with CML and MDA, but not with pyrraline. CONCLUSION: Our results suggest that glycoxidation and lipid peroxidation of LDL synergistically promote the development of atherosclerotic lesions through interaction with macrophage scavenger receptor-A.

Mutual alignment errors due to the variation of wave-front aberrations in a free-space laser communication link.

Optical devices in free-space laser communication systems are affected by their environment, particularly in relation to the effects of temperature while in orbit. The mutual alignment error between the transmitted and received optical axes is caused by deformation of the optics due to temperature variation in spite of the common optics used for transmission and reception of the optical beams. When a Gaussian beam wave for transmission is aligned at the center of a received plane wave, 3rd-order Coma aberrations have the most influence on the mutual alignment error, which is an inevitable open pointing error under only the Tip/Tilt tracking control. As an example, a mutual alignment error of less than 0.2 microrad is predicted for a laser communication terminal in orbit using the results from space chamber thermal vacuum tests. The relative power penalty due to aberration is estimated to be about 0.4 dB. The results will mitigate surface quality in an optical antenna and contribute to the design of free-space laser communication systems.

Nonoxidative protein glycation is implicated in familial amyotrophic lateral sclerosis with superoxide dismutase-1 mutation.

To assess a role for oxidative stress in the pathogenesis of amyotrophic lateral sclerosis (ALS), we analyzed the immunohistochemical localization of 8-hydroxy2'-deoxyguanosine (OHdG) as a nucleic acid oxidation product, acrolein-protein adduct and 4-hydroxy-2-nonenal (HNE)-protein adduct as lipid peroxidation products, Nepsiloncarboxymethyl-lysine (CML) as a lipid peroxidation or protein glycoxidation product, pentosidine as a protein glycoxidation product, and imidazolone and pyrraline as nonoxidative protein glycation products in the spinal cord of three familial ALS patients with superoxide dismutase(SOD 1) A4V mutation, six sporadic ALS patients, and six age-matched control individuals. The spinal cord sections of the control cases did not show any distinct immunoreactivities for these examined products. In the familial ALS cases, intense immunoreactivities for pyrraline and CML were confined to the characteristic Lewy body-like hyaline inclusions, and imidazolone immunoreactivity was located in the cytoplasm of the residual motor neurons. No significant immunoreactivities for other examined products were detected in the familial ALS spinal cords. In the sporadic ALS cases, intense immunoreactivities for pentosidine, CML and HNE-protein adduct were seen in the cytoplasm of the degenerated motor neurons, and OHdG immunoreactivity was located in the cell nuclei of the residual neurons and glial cells. The present results indicate that oxidative reactions are involved in the disease processes of sporadic ALS, while there is no evidence for increased oxidative damage except for CML deposition in the familial ALS spinal cords. Furthermore, it is likely that the accumulation of pyrraline and imidazolone supports a nonoxidative mechanism in SOD1-related motor neuron degeneration.

Glycoxidative modification of AA amyloid deposits in renal tissue.

BACKGROUND: N(epsilon)-carboxymethyllysine (CML) is a product of the oxidative modification of glycated proteins, which damages proteins with ageing, diabetes, uraemia and Alzheimer's disease. In contrast, pyrraline is one of the advanced glycation end products, which is independent of oxidative processes. CML has been identified in beta-amyloid of Alzheimer's disease and beta(2)-microglobulin-associated amyloid. We investigated whether CML and pyrraline are formed in AA and AL amyloid of the kidney. METHOD: Renal specimens from 19 cases of AA amyloidosis and 14 cases of AL amyloidosis were investigated for immunolocalization of CML, pyrraline, collagen type IV and laminin in amyloid deposits. Renal biopsies of 10 age-matched cases with thin basement membrane disease and normal renal function were used as controls. The fractional areas of amyloid, CML, laminin and collagen IV in glomeruli and interstitium (%amyloid, %CML, %laminin and %collagen, respectively) were calculated using the point counting method. The correlation between these parameters was evaluated using Spearman's rank correlation test. RESULTS: CML colocalized with AA amyloid, but not AL amyloid, except in two cases of the latter with a long history of nephropathy exceeding 14 years. In contrast, pyrraline was not observed in either type of amyloid. Mean %CML in AA amyloid was significantly higher than %collagen and %laminin in glomeruli and interstitium, indicating that AA amyloid is modified by CML independent of colocalized extracellular matrix. %CML significantly correlated with %amyloid both in glomeruli and interstitium in AA amyloidosis. AL amyloid cases with a long history of nephropathy showed positive staining for CML in glomeruli and interstitium but no staining for collagen IV and laminin in amyloid deposits. CONCLUSION: CML modification may occur in amyloid deposits of AA amyloidosis, independent of extracellular matrix components. Glycoxidative modification may have a functional link to AA amyloid deposition in renal tissues.