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Depalmitoylation preferentially downregulates AMPA induced Ca2+ signaling and neurotoxicity in motor neurons.
Brain Res. 2013 Sep 05; 1529:143-53.BR

Abstract

Excessive activation of AMPA receptor has been implicated in motor neuron degeneration in amyotrophic lateral sclerosis (ALS). However, it is not clear why motor neurons are preferentially sensitive to AMPA receptor mediated excessive [Ca(2+)]i rise and excitotoxicity. In the present study we examined whether palmitoylation regulates Ca(2+) permeability of AMPA receptor and excitotoxicity in cultured spinal cord neurons. We adapted chronic 2-bromopalmitate (2-BrP) treatment to achieve depalmitoylation and examined its effect on the cytotoxicity in spinal cord neurons exposed to AMPA. The change in AMPA induced signaling and cytotoxicity in motor neurons and other spinal neurons under identical conditions of exposure to AMPA was studied. 2-BrP treatment inhibited AMPA induced rise in [Ca(2+)]i and cytotoxicity in both types of neurons but the degree of inhibition was significantly higher in motor neurons as compared to other spinal neurons. The AMPA induced [Na(+)]i rise was moderately affected in both type of neurons on depalmitoylation. Depalmitoylation reduced the expression levels of AMPA receptor subunits (GluR1 and GluR2) and also PSD-95 but stargazin levels remained unaffected. Our results demonstrate that 2-BrP attenuates AMPA receptor activated Ca(2+) signaling and cytotoxicity preferentially in motor neurons and suggest that AMPA receptor modulation by depalmitoylation could play a significant role in preventing motor neuron degeneration.

Authors+Show Affiliations

Department of Biophysics, National Institute of Mental Health and Neuro Sciences, Bangalore 560029, India.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23850769

Citation

Krishnamurthy, Karthik, et al. "Depalmitoylation Preferentially Downregulates AMPA Induced Ca2+ Signaling and Neurotoxicity in Motor Neurons." Brain Research, vol. 1529, 2013, pp. 143-53.
Krishnamurthy K, Mehta B, Singh M, et al. Depalmitoylation preferentially downregulates AMPA induced Ca2+ signaling and neurotoxicity in motor neurons. Brain Res. 2013;1529:143-53.
Krishnamurthy, K., Mehta, B., Singh, M., Tewari, B. P., Joshi, P. G., & Joshi, N. B. (2013). Depalmitoylation preferentially downregulates AMPA induced Ca2+ signaling and neurotoxicity in motor neurons. Brain Research, 1529, 143-53. https://doi.org/10.1016/j.brainres.2013.06.039
Krishnamurthy K, et al. Depalmitoylation Preferentially Downregulates AMPA Induced Ca2+ Signaling and Neurotoxicity in Motor Neurons. Brain Res. 2013 Sep 5;1529:143-53. PubMed PMID: 23850769.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Depalmitoylation preferentially downregulates AMPA induced Ca2+ signaling and neurotoxicity in motor neurons. AU - Krishnamurthy,Karthik, AU - Mehta,Bhupesh, AU - Singh,Mahendra, AU - Tewari,Bhanu P, AU - Joshi,Preeti G, AU - Joshi,Nanda B, Y1 - 2013/07/10/ PY - 2012/09/12/received PY - 2013/06/24/revised PY - 2013/06/26/accepted PY - 2013/7/16/entrez PY - 2013/7/16/pubmed PY - 2014/3/19/medline KW - 2-BrP KW - 2-Bromopalmitate KW - AMPA KW - AMPA receptor KW - Amyotrophic lateral sclerosis KW - Calcium signaling KW - Depalmitoylation KW - EMEM KW - Eagle′s minimal essential medium KW - Excitotoxicity KW - HBSS KW - HEPES KW - Hanks buffered salt saline KW - Motor neuron KW - N-2-hydroxyethyl piperazine-n-2-ethanesulphonic acid KW - TARPs KW - Transmembrane AMPA receptor regulatory protein KW - Transmembrane AMPA receptor regulatory proteins KW - α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid SP - 143 EP - 53 JF - Brain research JO - Brain Res VL - 1529 N2 - Excessive activation of AMPA receptor has been implicated in motor neuron degeneration in amyotrophic lateral sclerosis (ALS). However, it is not clear why motor neurons are preferentially sensitive to AMPA receptor mediated excessive [Ca(2+)]i rise and excitotoxicity. In the present study we examined whether palmitoylation regulates Ca(2+) permeability of AMPA receptor and excitotoxicity in cultured spinal cord neurons. We adapted chronic 2-bromopalmitate (2-BrP) treatment to achieve depalmitoylation and examined its effect on the cytotoxicity in spinal cord neurons exposed to AMPA. The change in AMPA induced signaling and cytotoxicity in motor neurons and other spinal neurons under identical conditions of exposure to AMPA was studied. 2-BrP treatment inhibited AMPA induced rise in [Ca(2+)]i and cytotoxicity in both types of neurons but the degree of inhibition was significantly higher in motor neurons as compared to other spinal neurons. The AMPA induced [Na(+)]i rise was moderately affected in both type of neurons on depalmitoylation. Depalmitoylation reduced the expression levels of AMPA receptor subunits (GluR1 and GluR2) and also PSD-95 but stargazin levels remained unaffected. Our results demonstrate that 2-BrP attenuates AMPA receptor activated Ca(2+) signaling and cytotoxicity preferentially in motor neurons and suggest that AMPA receptor modulation by depalmitoylation could play a significant role in preventing motor neuron degeneration. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/23850769/Depalmitoylation_preferentially_downregulates_AMPA_induced_Ca2+_signaling_and_neurotoxicity_in_motor_neurons_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(13)00925-6 DB - PRIME DP - Unbound Medicine ER -