Title:Expression Analysis of 4-Hydroxynonenal Modified Proteins in Schizophrenia
Brain; Relevance to Involvement in Redox Dysregulation
Volume: 19
Issue: 1
Author(s): Sobia Manzoor, Ayesha Khan*, Beena Hasan, Shamim Mushtaq and Nikhat Ahmed
Affiliation:
- Neurochemistry Research Laboratory, Department of Biochemistry, University of Karachi, Karachi, Pakistan
Keywords:
Lipid peroxidation, polyunsaturated fatty acid, reduced glutathione, 4-hydroxynonenal, malondialdehyde, thiobarbituric acid reactive substances, catalase.
Abstract: Background: Oxidative damage contributes to the pathophysiology of schizophrenia
(SZ). Redox imbalance may lead to increased lipid peroxidation, which produces toxic aldehydes
like 4-hydroxynonenal (4-HNE) ultimately leading to oxidative stress. Conversely, implications of
oxidative stress point towards an alteration in HNE-protein adducts and activities of enzymatic and
antioxidant systems in schizophrenia.
Objectives: The present study focuses on the identification of HNE-protein adducts and their related
molecular consequences in schizophrenia pathology due to oxidative stress, particularly lipid
peroxidation.
Materials and Methods: Oxyblotting was performed on seven autopsied brain samples each from
the cortex and hippocampus region of schizophrenia patients and their respective normal healthy
controls. Additionally, Thiobarbituric Acid Substances (TBARS), reduced Glutathione (GSH) levels
and catalase (CAT) activities associated with oxidative stress, were also estimated.
Results: Obtained results indicate substantially higher levels of oxidative stress in schizophrenia patients
than healthy control group represented by elevated expression of HNE-protein adducts. Interestingly,
the hippocampus region of schizophrenia brain shows increased HNE protein adducts
compared to cortex. An increase in catalase activity (4.8876±1.7123) whereas a decrease in antioxidant
GSH levels (0.213±0.015μmol/ml) have been observed in SZ brain. Elevated TBARS levels
(0.3801±0.0532ug/ml) were obtained in brain regions of SZ patients compared with their controls
that reflect increased lipid peroxidation (LPO).
Conclusion: We propose the role of HNE modified proteins possibly associated with the pathology
of schizophrenia. Our data revealed increased lipid peroxidation as a consequence of increased
TBARS production. Furthermore, altered cellular antioxidants pathways related to GSH and CAT
also highlight the involvement of oxidative stress in schizophrenia pathology.
