Zinc down regulates Apaf-1-dependent Bax/Bcl-2 mediated caspases activation during aluminium induced neurotoxicity

Biometals (2015) 28:6173DOI 10.1007/s10534-014-9803-y

Zinc down regulates Apaf-1-dependent Bax/Bcl-2 mediated caspases activation during aluminium induced neurotoxicity

Neha Singla D. K. Dhawan

Received: 12 April 2014 / Accepted: 18 October 2014 / Published online: 9 November 2014 Springer Science+Business Media New York 2014

Abstract Aluminium (Al), a ubiquitous element in nature is associated with the onset of Alzheimers 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 140160 g were divided into four different groups viz: Normal control, Al treated (100 mg/kgb.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 signicant 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.

Keywords Aluminium Zinc Apoptosis

Ultrastructure Neurodegeneration Neurotoxicity

AbbreviationsAl AluminiumZn ZincRT-PCR Reverse transcription polymerase chain reactionDISC Death-inducing signaling complex CREB cAMP response element binding protein cyt c Cytochrome c

Introduction

From the last few decades, research is underway to explore various molecular mechanisms that are

N. Singla D. K. Dhawan (&)

Department of Biophysics, Sector-14, Panjab University, Chandigarh 160014, Indiae-mail: [email protected]

N. Singlae-mail: [email protected]

Present Address:N. SinglaDepartment of Biophysics, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India

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