Cellular Response against Oxidative Stress, a Novel Insight into Lupus Nephritis Pathogenesis

Abstract

The interaction of reactive oxygen species (ROS) with lipids, proteins, nucleic acids and hydrocarbonates promotes acute and chronic tissue damage, mediates immunomodulation and triggers autoimmunity in systemic lupus erythematous (SLE) patients. The aim of the study was to determine the pathophysiological mechanisms of the oxidative stress-related damage and molecular mechanisms to counteract oxidative stimuli in lupus nephritis. Our study included 38 SLE patients with lupus nephritis (LN group), 44 SLE patients without renal impairment (non-LN group) and 40 healthy volunteers as control group. In the present paper, we evaluated serum lipid peroxidation, DNA oxidation, oxidized proteins, carbohydrate oxidation, and endogenous protective systems. We detected defective DNA repair mechanisms via 8-oxoguanine-DNA-glycosylase (OGG1), the reduced regulatory effect of soluble receptor for advanced glycation end products (sRAGE) in the activation of AGE-RAGE axis, low levels of thiols, disulphide bonds formation and high nitrotyrosination in lupus nephritis. All these data help us to identify more molecular mechanisms to counteract oxidative stress in LN that could permit a more precise assessment of disease prognosis, as well as developing new therapeutic targets.

Advanced Glycation End-Products (AGEs) and Their Soluble Receptor (sRAGE) in Women Suffering from Systemic Lupus Erythematosus (SLE)

“…Chronic inflammation in SLE appears to be linked to an intensified glyco-oxidation process (also known as the glycation process) [ 11 , 14 ]. Advanced glycation end-products (AGEs) are formed during this complex reaction and can be recognized by the immune system as neoepitopes [ 15 , 16 , 17 ].…”

“…Current findings on the concentrations of AGEs in SLE patients are sparse. To date, the total concentration of AGEs in blood samples has been evaluated in two studies (using ELISA assay) [ 14 , 22 ]. Two more studies used the skin autofluorescence method [ 11 , 27 ].…”

“…Only one study included a group consisting solely of women ( n = 9) [ 11 ]. Regardless of the method used, increased concentrations of AGEs among SLE patients compared to the healthy control group were noted in all these studies [ 11 , 14 , 22 , 27 ].…”

“…Despite the wide range of compounds participating in the glycation process, there are few available studies focused on the evaluation of concentrations of individual compounds in SLE patients. These include studies concerning CML ( n = 9), CEL ( n = 9 and n = 40), pentosidine ( n = 37 and n = 82), fructosamine ( n = 37), and an unidentified product of ribose and protein reaction ( n = 40) [ 11 , 14 , 21 , 22 , 27 , 28 ]. A marginal increase in fructosamine concentration and contradictory results related to pentosidine concentration in the blood serum of SLE patients have been noted so far [ 14 , 28 ].…”

Serum Sialylation Changes in Actinic Keratosis and Cutaneous Squamous Cell Carcinoma Patients

“…We have previously investigated sialoglycoconjugate abnormalities and anti-ganglioside immune response as possible mechanisms involved in oncogenesis (cutaneous melanoma [ 23 ], clear cell renal cell carcinoma [ 34 ]), autoimmune diseases (systemic lupus erythematosus, lupus nephritis [ 35 ]), and diabetes [ 36 ]. Increased sialylation in melanoma cells could represent an event associated with the progression of cutaneous melanoma [ 17 ].…”