Academic journal article Indian Journal of Psychiatry

Role of Membrane Cholesterol and Lipid Peroxidation in Regulating the Na[sup]+/K[sup]+-ATPase Activity in Schizophrenia

Academic journal article Indian Journal of Psychiatry

Role of Membrane Cholesterol and Lipid Peroxidation in Regulating the Na[sup]+/K[sup]+-ATPase Activity in Schizophrenia

Article excerpt

Byline: Suparna. Roy, Anindya. Dasgupta, Ushasi. Banerjee, Piali. Chowdhury, Ashis. Mukhopadhyay, Gautam. Saha, Omprakash. Singh

Background: Na[sup]+/K[sup]+-ATPase (NKA) activity is compromised in several neuropsychiatric disorders. Oxidative stress and membrane lipid composition play important roles in regulating NKA activity. Aims: The present study was undertaken to evaluate the effects of oxidative stress-induced membrane lipid damage and membrane cholesterol composition on NKA pump activity in schizophrenia. Settings and Design: It was a hospital-based, cross-sectional, observational study in 49 cases and 51 controls for 1 year. Materials and Methods: NKA pump activity in red blood cell membrane, serum levels of thiobarbituric acid reactive substances (TBARS), protein carbonyl (PC) adducts, and cholesterol were measured by standard spectrophotometric techniques in newly diagnosed schizophrenia patients by Diagnostic and Statistical Manual of Mental Disorders, 4[sup]th Edition, Text Revision criteria. Membrane cholesterol was analyzed by chloroform and isopropanol extraction followed by measuring the cholesterol concentration by spectrophotometric technique. Statistical Analysis and Results: Mean values for NKA pump activity, membrane cholesterol level, and serum cholesterol levels were significantly lower in the case group (P < 0.001). The activity of NKA pump was found to be directly correlated to membrane cholesterol level rather than with the serum cholesterol values. Although the NKA pump activity showed inverse relationship with the serum values of TBARS and PC products both, on multiple linear regression analysis, it was found to be significantly positively dependent on the membrane cholesterol ([sz] = 0.268, P = 0.01) and negatively dependent on the serum TBARS ([sz] = −0.63, P < 0.001) levels only. Conclusion: Reduced membrane cholesterol and oxidative stress-induced damage to membrane lipids play crucial roles in decreasing the NKA activity in schizophrenia. Hence, for a better prognosis and treatment, measures are required to maintain optimum levels of cholesterol in neuronal tissues along with a proper control on oxidative stress.

Introduction

The Na [sup]+/K [sup]+-ATPase (NKA) is a ubiquitous enzyme that maintains the Na [sup]+ and K [sup]+ gradients across the cell membrane by transporting three Na [sup]+ out and two K [sup]+ into the cell. It is necessary for proper cellular function since it helps to preserve the ionic gradients across the cell membrane and thus the membrane potential and osmotic equilibrium of the cell.[sup][1] Structural variations of this pump are notable which is supposed to contribute significantly in its regulation by different modulators. This pump has one principal catalytic subunit termed a subunit, one sugar-rich auxiliary [sz] subunit, and sometimes a a subunit. The a subunits have 10 transmembrane segments known as FXYD segments, with variable binding affinity for different regulator or modulators, particularly the lipid molecules. Several lipids have been found to influence its activity through binding at different sites of this oligomeric protein pump. Phospholipids such as phosphatidylcholine (PC) and phosphatidylethanolamine enhance the activity of the pump by promoting the conformational change from E1 to E2 (P) by reacting with the surface charges of this integral membrane protein [sup][2] while some other such as phosphatidylserine (PS) helps in stabilizing the pump by binding critical Ile and Lys residues in the hydrophobic core of the FXYD a helices [sup][3],[4]. Moreover, a specific interaction of this pump with 18:0/18:1 PS (1-stearoyl-2-oleoyl-sn-glycero-3-phospho-L-serine) and cholesterol was found to help its thermal stability significantly.[sup][5] However, so far, cholesterol has been suggested to be the only membrane lipid component that is found to be resolved in NKA structures.[sup][2] Maintenance of native NKA structure is strongly dependent on cholesterol. …

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