4-Hydroxynonenal (HNE), a major end-product of free-radical activated peroxidation of polyunsaturated fatty acids, has attracted great scientific interest. HNE is more stable than free radicals and can diffuse within the cell or leave it and react with targets far from the initial site. These reactive aldehyde species are considerably reactive, producing multiple intra-and inter-molecular covalent adducts with biomolecules such as proteins, DNA and phospholipids. HNE is the most intensively studied aldehyde in relation to its physiological and protective function as a signalling molecule that stimulates gene expression and cell survival, as well as for its pathophysiological role as a toxic messenger that can propagate and amplify oxidative injury and promote mitochondrial dysfunction and cell death. Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease in the world associated with oxidative stress, mitochondrial dysfunction and hepatocellular apoptosis. In this review we focus our attention on the molecular mechanism of the signalling and regulatory action of HNE. The role of HNE as a potent mediator for progression of liver injury in NAFLD is also discussed.

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INTRODUCTION: Lupus nephritis (LN) is a serious complication of the systemic lupus erythematosus (SLE). Anti-C1q antibodies correlate with the occurrence and high clinical activity of LN, especially proliferative LN. The first reported anti-C1q antibodies recognized autoepitopes within a collagen-like region (CLR) of C1q. Recently we have found autoantibodies against globular C1q domain (gC1q antibodies) in LN patients. The aim of the present study was to evaluate the potential pathological consequences of the presence of anti-gC1q antibodies in LN. MATERIAL AND METHODS: The recombinant globular head region of the three chains of C1q -A, -B and -C were expressed in E. coli BL21 and purified. Anti-C1q, anti-gC1q autoantibodies, complement proteins -C1q, C4, C3 and IgG-, IgM-CICs levels were screened by ELISA in 53 sera from LN patients. Sera from 196 normal controls served as controls. C1q antibodies (p=0.005; p=0.018). Significant correlations to IgG CICs were detected for anti- C1q (r=0.371, p=0.001) and anti-B-gC1q antibodies (r=0.431, p=0.003). RESULTS: We found that patients positive for anti-B-gC1q antibodies presented with significantly lower serum C4 levels than patients positive for anti-A and anti-C-gC1q antibodies (p=0.014) and with significantly lower levels of C3 than patients positive for anti-A and anti-C-gC1q antibodies and patients without anti- CONCLUSIONS:These findings suggest that the binding of anti-B-gC1q autoantibodies with C1q may possibly trigger mechanical stress and induce a structural change within the CLR domain of C1q, compatible with C1r-C1s complement activation in the fluid phase.

Rs292001 is single nucleotide polymorphism in non-coding regions of the C1QA gene. C1q is a subcomponent of the C1 first component of the classical pathway of complement activation. Rs292001 was investigated for an association with some conventional immunological markers of lupus nephritis (LN) activity in systemic lupus erythematosus (SLE) patients -levels of C1q, C3, C4, anti-C1q, anti-nuclear (ANA) and anti-ds-DNA autoantibodies.Genomic DNA was isolated from peripheral blood of 18 patients with biopsy-proven LN. SNP genotyping for the presence of rs292001 was performed by quantitative real-time PCR method. Presence of complement C1q, C3 and C4 and anti-C1q autoantibodies was screened by ELISA. ANA and anti-dsDNA antibodies were detected by double immunodiffusion assays and indirect immunofluorescence.We found that the GG rs292001 genotype prevailed in seronegative for ANA and anti-dsDNA antibodies LN patients (p=0.008; p<0.012). The AA rs292001 genotype showed a trend towards lower serum C1q levels.These results reaffirm a previously established probable protective role of the G allele against the clinical activity of the SLE.