Top

Published in:

01-05-2016 | Translational Neurosciences - Short communication

Rasagiline prevents cyclosporine A-sensitive superoxide flashes induced by PK11195, the initial signal of mitochondrial membrane permeabilization and apoptosis

Authors: Yuqiu Wu, Masayo Shamoto-Nagai, Wakako Maruyama, Toshihiko Osawa, Makoto Naoi

Published in: Journal of Neural Transmission | Issue 5/2016

Abstract

Rasagiline, a neuroprotective inhibitor of type B monoamine oxidase, prevented PK111195-induced apoptosis in SH-SY5Y cells through inhibition of mitochondrial apoptosis signaling (J Neural Transm 120:1539–1551, 2013, J Neural Transm 122:1399–1407, 2015). This paper presents that PK11195 induced superoxide flashes, the transit production burst, mediated by cyclosporine A-sensitive membrane permeability transition. Rasagiline prevented superoxide flashes, calcium efflux, and cell death by PK11195. Regulation of the initial pore formation at the inner mitochondrial membrane was confirmed as the decisive mechanism of neuroprotection by rasagiline.

Akao Y, Maruyama W, Shimizu S, Yi H, Shamoto-Nagai M, Youdim MB, Tsujimoto Y, Naoi M (2002) Mitochondrial permeability transition mediates apoptosis induced by N-methyl(R)salsolinol, an endogenous neurotoxin, and its inhibited by Bcl-2 and rasagiline, N-propargyl-1(R)-aminoindan. J Neurochem 82(4):913–923CrossRefPubMed

Bar-Am O, Amit T, Youdim MB, Weinreb O (2016) Neuroprotective and neurorestorative potential of propargylamine derivatives in ageing: focus on mitochondrial targets. J Neural Transm 133(2):125–135CrossRef

Czerniczyniec A, Bustamante J, Lores-Arnaiz S (2006) Modulation of brain mitochondrial function by deprenyl. Neurochem Int 48(3):235–241CrossRefPubMed

Finberg JPM (2010) Pharmacology of rasagiline, a new MAO-B inhibitor drug for the treatment of Parkinson’s disease with neuroprotective potential. Rambam Maimonides Med J 1(1):e0003CrossRefPubMedPubMedCentral

Hou T, Wang X, Ma Q, Cheng H (2014) Mitochondrial flashes: new insights into mitochondrial ROS signaling and beyond. J Physiol 592(17):3703–3713CrossRefPubMedPubMedCentral

Jenner P, Langston JW (2011) Explaining ADAGIO: a critical review of the biological basis for the clinical effects of rasagiline. Mov Disord 26(12):2316–2323CrossRefPubMed

Kroemer G, Galluzzi L, Brenner C (2007) Mitochondrial membrane permeabilization in cell death. Physiol Rev 87:99–163CrossRefPubMed

Nakano M, Sugiola K, Ushujima Y, Goto T (1989) Chemiluminescence probe with Cypidina luciferin analog, 2-methyl-6-phenyl-3,7-dihydroimidazo- [1,2-a]pyrazin-3-one, for estimating the ability of human granulocytes to generate O₂ ^.−. Anal Biochem 159(2):363–369CrossRef

Naoi M, Maruyama W, Yi H (2013) Rasagiline prevents apoptosis induced by PK11195, a ligand of the outer membrane translocator protein (18 kDa), in SH-SY5Y cells through suppression of cytochrome c release from mitochondria. J Neural Transm 120(11):1539–1551CrossRefPubMed

Wu Y, Kazumura K, Maruyama W, Osawa T, Naoi M (2015) Rasagiline and selegiline suppress calcium efflux from mitochondria by PK11195-induced opening of mitochondrial permeability transition pore: a novel antiapoptotic function for neuroprotection. J Neural Transm 122(10):1399–1407CrossRefPubMed

Title: Rasagiline prevents cyclosporine A-sensitive superoxide flashes induced by PK11195, the initial signal of mitochondrial membrane permeabilization and apoptosis
Authors: Yuqiu Wu
Masayo Shamoto-Nagai
Wakako Maruyama
Toshihiko Osawa
Makoto Naoi
Publication date: 01-05-2016
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 5/2016
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-016-1531-8

At a glance: The STEP trials

Springer Medicine

Rasagiline prevents cyclosporine A-sensitive superoxide flashes induced by PK11195, the initial signal of mitochondrial membrane permeabilization and apoptosis

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 5/2016

Nigral involvement in atypical parkinsonisms: evidence from a pilot study with ultra-high field MRI

Quantification of sound instability in embouchure tremor based on the time-varying fundamental frequency

Comparison of baroreflex sensitivity estimated from ECG R–R and inter-systolic intervals obtained by finger plethysmography and radial tonometry

Botulinum toxin therapy: reduction of injection site pain by pH normalisation

Reconstituting botulinum toxin drugs: shaking, stirring or what?

Secondary task performance during challenging walking tasks and freezing episodes in Parkinson’s disease