Axonal Degeneration in Retinal Ganglion Cells Is Associated with a Membrane Polarity-Sensitive Redox Process

被引:32
作者
Almasieh, Mohammadali [1 ,2 ,3 ,4 ]
Catrinescu, Maria-Magdalena [1 ,2 ]
Binan, Loic [1 ,2 ]
Costantino, Santiago [1 ,2 ]
Levin, Leonard A. [1 ,2 ,3 ,4 ,5 ]
机构
[1] Univ Montreal, Maisonneuve Rosemont Hosp Res Ctr, Montreal, PQ H1T 2M4, Canada
[2] Univ Montreal, Dept Ophthalmol, Montreal, PQ H1T 2M4, Canada
[3] McGill Univ, Dept Ophthalmol, Montreal, PQ H4A 3S5, Canada
[4] McGill Univ, Dept Neurol, Montreal, PQ H4A 3S5, Canada
[5] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI 53706 USA
基金
美国国家卫生研究院; 加拿大自然科学与工程研究理事会;
关键词
axon membrane; axonal degeneration; phosphatidylserine; redox; Wallerian degeneration slow; SLOW WALLERIAN DEGENERATION; PHOSPHOLIPID SCRAMBLASE; SELF-DESTRUCTION; OPTIC-NERVE; WILD-TYPE; IN-VITRO; PHOSPHATIDYLSERINE; AXOTOMY; DEATH; ASYMMETRY;
D O I
10.1523/JNEUROSCI.3882-16.2017
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Axonal degeneration is a pathophysiological mechanism common to several neurodegenerative diseases. The slow Wallerian degeneration (WldS) mutation, which results in reduced axonal degeneration in the central and peripheral nervous systems, has provided insight into a redox-dependent mechanism by which axons undergo self-destruction. We studied early molecular events in axonal degeneration with single-axon laser axotomy and time-lapse imaging, monitoring the initial changes in transected axons of purified retinal ganglion cells (RGCs) from wild-type and Wld(S) rat retinas using a polarity-sensitive annexin-based biosensor (annexin B12-Cys101, Cys260-N, N'-dimethyl- N-(iodoacetyl)-N'-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) ethylenediamine). Transected axons demonstrated a rapid and progressive change in membrane phospholipid polarity, manifested as phosphatidylserine externalization, which was significantly delayed and propagated more slowly in axotomized Wld(S) RGCs compared with wild-type axons. Delivery of bis(3-propionic acid methyl ester) phenylphosphine borane complex, a cell-permeable intracellular disulfide-reducing drug, slowed the onset and velocity of phosphatidylserine externalization in wild-type axons significantly, replicating the WldS phenotype, whereas extracellular redox modulation reversed the Wld(S) phenotype. These findings are consistent with an intra-axonal redox mechanism for axonal degeneration associated with the initiation and propagation of phosphatidylserine externalization after axotomy.
引用
收藏
页码:3824 / 3839
页数:16
相关论文
共 95 条
[1]   A rat model of slow Wallerian degeneration (WldS) with improved preservation of neuromuscular synapses [J].
Adalbert, R ;
Gillingwater, TH ;
Haley, JE ;
Bridge, K ;
Beirowski, B ;
Berek, L ;
Wagner, D ;
Grumme, D ;
Thomson, D ;
Celik, A ;
Addicks, K ;
Ribchester, RR ;
Coleman, MP .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2005, 21 (01) :271-277
[2]   INTRA-AXONAL CALCIUM CHANGES AFTER AXOTOMY IN WILD-TYPE AND SLOW WALLERIAN DEGENERATION AXONS [J].
Adalbert, R. ;
Morreale, G. ;
Paizs, M. ;
Conforti, L. ;
Walker, S. A. ;
Roderick, H. L. ;
Bootman, M. D. ;
Siklos, L. ;
Coleman, M. P. .
NEUROSCIENCE, 2012, 225 :44-54
[3]   A cell-permeable phosphine-borane complex delays retinal ganglion cell death after axonal injury through activation of the pro-survival extracellular signal-regulated kinases 1/2 pathway [J].
Almasieh, Mohammadali ;
Lieven, Christopher J. ;
Levin, Leonard A. ;
Di Polo, Adriana .
JOURNAL OF NEUROCHEMISTRY, 2011, 118 (06) :1075-1086
[4]   Selective Targeting of ER Exit Sites Supports Axon Development [J].
Aridor, Meir ;
Fish, Kenneth N. .
TRAFFIC, 2009, 10 (11) :1669-1684
[5]   WldS Prevents Axon Degeneration through Increased Mitochondrial Flux and Enhanced Mitochondrial Ca2+ Buffering [J].
Avery, Michelle A. ;
Rooney, Timothy M. ;
Pandya, Jignesh D. ;
Wishart, Thomas M. ;
Gillingwater, Thomas H. ;
Geddes, James W. ;
Sullivan, Patrick G. ;
Freeman, Marc R. .
CURRENT BIOLOGY, 2012, 22 (07) :596-600
[6]   Regulated externalization of phosphatidylserine at the cell surface - Implications for apoptosis [J].
Balasubramanian, Krishnakumar ;
Mirnikjoo, Banafsheh ;
Schroit, Alan J. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (25) :18357-18364
[7]   IMMUNOLOGICAL, MORPHOLOGICAL, AND ELECTROPHYSIOLOGICAL VARIATION AMONG RETINAL GANGLION-CELLS PURIFIED BY PANNING [J].
BARRES, BA ;
SILVERSTEIN, BE ;
COREY, DP ;
CHUN, LLY .
NEURON, 1988, 1 (09) :791-803
[8]   Axonal Degeneration Is Mediated by the Mitochondrial Permeability Transition Pore [J].
Barrientos, Sebastian A. ;
Martinez, Nicolas W. ;
Yoo, Soonmoon ;
Jara, Juan S. ;
Zamorano, Sebastian ;
Hetz, Claudio ;
Twiss, Jeffery L. ;
Alvarez, Jaime ;
Court, Felipe A. .
JOURNAL OF NEUROSCIENCE, 2011, 31 (03) :966-978
[9]   EXTENSIVE ELONGATION OF AXONS FROM RAT-BRAIN INTO PERIPHERAL-NERVE GRAFTS [J].
BENFEY, M ;
AGUAYO, AJ .
NATURE, 1982, 296 (5853) :150-152
[10]   ALTERATIONS IN MEMBRANE-POTENTIAL AFTER AXOTOMY AT DIFFERENT DISTANCES FROM THE SOMA OF AN IDENTIFIED NEURON AND THE EFFECT OF DEPOLARIZATION ON NEURITE OUTGROWTH AND CALCIUM-CHANNEL EXPRESSION [J].
BERDAN, RC ;
EASAW, JC ;
WANG, R .
JOURNAL OF NEUROPHYSIOLOGY, 1993, 69 (01) :151-164