Role of membrane cholesterol and lipid peroxidation in regulating the Na⁺/K⁺-ATPase activity in schizophrenia

Abstract

Background:Na+/K+-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, 4th 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 (β = 0.268, P = 0.01) and negatively dependent on the serum TBARS (β = −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.

Nutritional ketosis as an intervention to relieve astrogliosis: Possible therapeutic applications in the treatment of neurodegenerative and neuroprogressive disorders

“…The dependence of K + uptake into astrocytes on NKA activity goes some way to explaining evidence supplied by several authors confirming that the maintenance of K + homeostasis is the most energy intensive role of astrocytes [249] and thus dependent on adequate supplies of ATP [250,251]. The function of NKA and its indispensable role in astrocyte is well documented and hence will not be considered here but any readers interested in a detailed consideration of the biochemistry underpinning its structure and functions are referred to excellent reviews by Roy et al [245] and Rodrigo et al [252].…”

“…Glutamate and GABA uptake are energy consuming processes as previously discussed [199,243] due in part to the reliance of EAATs on the option function of NKA receptors which coexist in the same molecular complex [244] (reviewed by [243]). This enzyme, as the name suggests, is in turn dependent on adequate supplies of ATP [245] and hence its function is likely to be compromised in an environment of impaired bioenergetics characteristic of astrocytes in their reactive state [55].…”

The Contribution of Fluoride to the Pathogenesis of Eye Diseases: Molecular Mechanisms and Implications for Public Health

“…Previous studies have shown that inhibition of Na+, K+-ATPase activity has been found to accelerate depletion of adenosine triphosphate (ATP), induce mitochondrial depolarization, suppress reactive oxygen species (ROS) scavenging, and enhance ROS production and oxidative stress [ 122 , 123 , 124 ]. Loss of Na+, K+-ATPase activity is associated with cataract formation [ 125 , 126 , 127 , 128 , 129 ] and age-dependent degeneration in photoreceptors [ 130 ]; suggesting a link between loss of Na+, K+-ATPase and AMD.…”

Fluoride Exposure Induces Inhibition of Sodium-and Potassium-Activated Adenosine Triphosphatase (Na+, K+-ATPase) Enzyme Activity: Molecular Mechanisms and Implications for Public Health

“…Previous studies have shown that inhibition of NKA activity has been found to accelerate depletion of adenosine triphosphate (ATP), induce mitochondrial depolarization, suppress reactive oxygen species (ROS) scavenging, and enhance ROS production and oxidative stress [15,16,17]. It is known that a causal relationship has been identified between NKA enzyme inhibition and airway hyperreactivity [18].…”