Zinc down regulates Apaf-1-dependent Bax/Bcl-2 mediated caspases activation during aluminium induced neurotoxicity.
Aluminium (Al), a ubiquitous element in nature is associated with the onset of Alzheimer's disease. On the other hand, zinc (Zn) is an essential trace element that regulates large number of physiological processes in the human body. The present study was conducted to explore the role of zinc, if any, in regulating apoptotic machinery during Al induced neurodegeneration in rat. Male sprague dawley rats weighing 140-160 g were divided into four different groups viz: Normal control, Al treated (100 mg/kg b.wt./day), Zn treated (227 mg/l) and combined Al and Zn treated. All the treatments were carried out for a total duration of 8 weeks. Al treatment resulted in a significant increase in the protein expressions of cytochrome c, Bax, Apaf-1, caspase 9, caspase 3 (p17), caspase 8, caspase 6, caspase 7 but decreased the Bcl-2 in both the cerebrum and cerebellum. However, Zn supplementation to Al treated rats resulted in a reduction in the protein expressions of cytochrome c, Bax, Apaf-1, caspase 9, caspase 3 (p17), caspase 8, caspase 6 and caspase 7 whereas it elevated the Bcl-2 in both the regions. Further, gene expressions of caspase 3 and caspase 9 were also found to be elevated after Al treatment, which however were reduced following Zn co-treatment. The electron-microscopic analysis of brain revealed that Al intoxication resulted in a number of degenerative signs at ultrastructural level, which were appreciably improved upon Zn supplementation. The present study suggests that Zn provides protection against Al induced neurotoxicity by triggering anti-apoptotic machinery.
Department of Biophysics, Sector-14, Panjab University, Chandigarh, 160014, India, nehasbph@gmail.com.
Neha
N
Singla
D K
DK
Dhawan
D000535:Aluminum / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053178:Caspase 6 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D054022:Cerebrum / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D008297:Male; D046529:Microscopy, Electron, Transmission; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015032:Zinc / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D000535:Aluminum; D053148:Caspase 3; D053178:Caspase 6; D053179:Caspase 7; D015032:Zinc