Oxidative modifications of plasma proteins and decreased leukocyte mitochondrial DNA of schizophrenia patients

OBJECTIVES: Schizophrenia is the most frequent and the most important psychiatric disorder. Although the dopaminergic dysfunction is considered as the main pathophysi-ologic feature of schizophrenia, the exact mechanism leading to dopaminergic dysfunction is still unclear. Different genetic and environmental causative risk factors for schizophrenia have been identified. Despite the strong heterogeneity of the risk factors, oxidative stress could represent the underlying biological mechanism linking these risk factors.METHODS: We have investigated oxidative modifications of plasma proteins by fluorescent spectroscopy. The conjugates of plasma proteins with 4-hydroxynonenal were determined by Western blot analysis. Relative content of mitochondrial DNA in leukocytes of the patients with confirmed diagnosis of schizophrenia was determined by real time PCR.RESULTS: We have shown decreased fluorescence of aromatic amino acid residues of plasma proteins and decreased level of mitochondrial DNA in leukocytes of patients suffering from schizophrenia. In addition, we have documented altered pattern of plasma proteins modified with 4-hydroxynonenal.CONCLUSION: Our results support an idea about important link between oxidative stress, mitochondrial dysfunction and schizophrenia. Although cause consequence relationships are not clear, it seems that mechanism associated with oxidative stress and mitochondrial functions can serve as important targets for development of new strategies to treat schizo-phrenia.