Neurofilament phosphorylation and disruption: a possible mechanism of chronic aluminium toxicity in Wistar rats.
The present study was designed to investigate the possible effects of chronic aluminium exposure on neurofilament phosphorylation and its subsequent disruption in various regions of the rat brain. An intra-gastric dose of aluminium (10mg/kg bw for 12 weeks) resulted in a marked enhancement of Ca2+/CaM dependent protein kinase activity as compared to cAMP dependent protein kinase. The levels of phosphoprotein phosphatase were found to be significantly depleted only in the cerebral cortex. After in vitro phosphorylation using [32gamma-P] ATP, various proteins were resolved on one-dimensional 8% SDS-PAGE, stained with Coomassie Blue and autoradiographed. The amount of 32P-incorporated was quantified using ADOPE PHOTOSHOP (7.0). The 200 kDa neurofilament protein was identified using immunoblotting. Finally, the extent of phosphorylation induced neurofilamentous damage was assessed using immunocytochemical studies. The cytoskeletal proteins were found to be aggregated and disrupted in all the three neuronal regions following 12 weeks of aluminium treatment. This study lends further support to the possible role of aluminium as a potent neurotoxic agent and in the etiopathogenisis of various neurodegenerative diseases.
Kaur
Amarpreet
A
Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India.
Joshi
Kusum
K
Minz
Ranjana Walker
RW
Gill
Kiran Dip
KD
D000535:Aluminum / Q000633:toxicity*; D000818:Animals; D001345:Autoradiography; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000473:pathology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D004591:Electrophoresis, Polyacrylamide Gel; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D008568:Memory / Q000187:drug effects; D016900:Neurofilament Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D004856:Postural Balance / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D016900:Neurofilament Proteins; D000535:Aluminum; D017868:Cyclic AMP-Dependent Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases