1Biochemistry Division; Indian Council of Medical Research, Hyderabad, India
2Division of Pathology National Institute of Nutrition, Indian Council of Medical Research, Hyderabad, India
3Biochemistry Division; Indian Council of Medical Research, Hyderabad, India
4Biochemistry Division; Indian Council of Medical Research, Hyderabad, India
Aluminium induced neurotoxicity is an important associated factor for the morbidity and mortality in Alzheimers Dementia (AD) and in some form of renal disorders where aluminium excretion is compromised. The present study was undertaken to investigate the effects of aluminium in vitro on certain key enzymes of rat brain and also parameters of synaptosomal integrity and function.
Three adult male WNIN rats aged three to four months were used for all the in vitro investigations which included, mitochondrial glucose utilization, respiration rate, membrane integrity, neurotransmitter reuptake and ATP dependent transport mechanisms, phosphorylation reactions involving cytoskeletal proteins, changes in membrane permeability/transport and intracellular calcium homeostasis. To study the inhibitory effects of aluminium on various enzymes, the enzyme inhibitor constant (Ki) was calculated.
In the present study, aluminum is found to be a potent noncompetitive inhibitor of brain hexokinase, succinate dehydrogenase & malate dehydrogenase as also of membrane bound protein kinase C (PKC) and synaptosomal calcium influx under depolarizing conditions.
The aluminum induced neurotoxicity could be partly mediated through its inhibitory effects on certain enzymes which are involved in the glucose catabolism, mitochondrial respiration, neurotransmitter reuptake and inorganic phosphate release in addition to its effects on synaptosomal Ca2+ uptake.
Aluminium, inhibitor constant, neurotransmitter reuptake, rat brain enzymes, synaptosome
