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Abstract

1. The authors compare oxidative injury to brain and kidney Na/K-ATPase using in vitro and in vivo approaches. The substrate dependence of dog kidney Na/K-ATPase was examined both before and after partial hydrogen peroxide modification. A computer simulation model was used for calculating kinetic parameters. 2. The substrate dependence curve for the unmodified endogenous enzyme displayed a typical curve with an intermediate plateau, adequately described by the sum of hyperbolic and sigmoidal components. 3. The modified enzyme demonstrated a dependent curve that closely approximates normal hyperbola. The estimated ATP K(m) value for the endogenous enzyme was about 85 microM; the Kh was equal to 800 microM. The maximal number of protomers interacting was 8. Following oxidative modification, the enzyme substrate dependence curve did not show a significant change in the maximal protomer rate Vm, while the K(m) was increased slightly and interprotomer interaction was abolished. 4. Na/K-ATPase from an ischemic gerbil brain showed a 22% decrease in specific activity. The maximal rate of ATP hydrolysis by an enzyme protomer changed slightly. but the sigmoidal component, characterizing the enzyme's ability to form oligomers was abolished completely. The K(m) value was almost unchanged, but the Hill coefficient fell to 1. These data show that Na/K-ATPase molecules isolated from the ischemic brain have lost the ability to interact with one another. 5. We suggest that the most important consequence of oxidative modification is Na/K-ATPase oligomeric structure formation and subsequent hydrolysis rate suppression.

Chronic Dietary Supplementation of 4% Figs on the Modification of Oxidative Stress in Alzheimer’s Disease Transgenic Mouse Model

“…In the current study, the activity of Na + K + ATPase was found to be decreased in AD Tg mice, which is in line with other studies reporting decrease in the enzyme activity during aging [70, 71]. Na + K + ATPase is known to be highly susceptible to changes in the membrane lipids, which may be further attributed to the progressive increase in the lipid peroxidation [72, 73]. ROS overproduction inhibits the activity of ATPase via thiol- and lipid-dependent mechanisms [74].…”

Effect of pomegranate extracts on brain antioxidant markers and cholinesterase activity in high fat-high fructose diet induced obesity in rat model

“…One of the possible mechanisms of neuroprotective effect of punicalagin was an improvement of Na+/K+ ATPase activity, an integral membrane protein which maintains electrolyte and fluid balance in cells, organs, and the whole body [54]. ATPase is known to be highly susceptible to changes in the membrane lipids, which may be further attributed to the progressive increase in the Lipid peroxidation (LPO) products especially MDA levels [55, 56]. Modification in Na + K + −ATPase activity may induce neuronal death with features of both apoptosis and necrosis [57].…”

Pomegranate from Oman Alleviates the Brain Oxidative Damage in Transgenic Mouse Model of Alzheimer’s Disease

“…[5253] Na + K + -ATPase is known to be highly susceptible to changes in the membrane lipids, which may be further attributed to the progressive increase in the LPO. [5455] ROS overproduction inhibits the activity of ATPase via thiol- and lipid-dependent mechanisms. [56] It has been demonstrated that the reduced activity of Na + K + -ATPase caused by oxidative stress cannot drive the ion pumps to maintain depolarization of neurons and, thus, may become lethal to neurons.…”