The involvement of purinergic signaling in mitochondria dysfunction induced by Alpha-synuklein

• Autorzy: Lenkiewicz A.M. , Wilkaniec A. , Adamczyk A.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: The purinergic P2 receptors for adenosine 5’-triphosphate (ATP) have been shown to be involved in neurodegenerative disorders including Parkinson’s (PD) and Alzheimer’s diseases (AD). However, the mechanisms underlying the disturbances in ATP-mediated neurotransmission is not clear. Our previous studies support the idea that α-Synuclein (ASN) oligomerisation and its intercellular spreading play a pivotal role in progressive development of these neurodegenerative disorders. Therefore, the aim of our study is to examine the role of purinergic P2 receptors in extracellular ASN evoked mitochondria dysfunction and cell death. METHODS: The experiments were performed in human SH-SY5Y neuroblastoma cells differentiated with the all-trans retinoic acid (ATRA) using immunochemical, spectrophotometrical, radiochemical and spectrofluorometrical methods. RESULTS: Our study showed that exogenously added ASN (10 µM) induces release of ATP from SH-SY5Y cells leading to activation of P2 receptors and extracellular Ca2+ influx. Moreover, ASN treatment results in mitochondria dysfunction manifested by decrease of intracellular ATP level and dysregulation of mitochondria enzymes expression. All mentioned dysfunctions lead to SH-SY5Y cell death. It was demonstrated hat selective purinergic P2 receptors antagonist, PPADS (200 µM), significantly prevented ASN-evoked Ca2+ influx, decrease of intracellular ATP level and SH-SY5Y cell death. CONCLUSIONS: Summarizing, ASN may exerts its toxic effect via purinergic P2 receptors activation leading to impairment of calcium homeostasis, mitochondria dysfunction and cell death. We suggest that the P2 signaling pathway could be a therapeutic target for ASN toxicity in neurodegenerative disorders. Supported by NCN grants: 2013/09/D/NZ3/01359 to A.W. and 2012/05/B/NZ3/02047 to A.A.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S99

Twórcy

autor

Lenkiewicz A.M.

• Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Wilkaniec A.

• Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Adamczyk A.

• Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland