BmK NSP, a new sodium channel activator from Buthus martensii Karsch, promotes neurite outgrowth in primary cultured spinal cord neurons

Toxicon ◽  
2020 ◽  
Vol 182 ◽  
pp. 13-20
Author(s):  
Xiaohan Zou ◽  
Yujing Wang ◽  
Yiyi Yu ◽  
Jing He ◽  
Fang Zhao ◽  
...  
Toxins ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 33
Author(s):  
Fang Zhao ◽  
Xiaohan Zou ◽  
Shaoheng Li ◽  
Jing He ◽  
Chuchu Xi ◽  
...  

Scorpion toxins represent a variety of tools to explore molecular mechanisms and cellular signaling pathways of many biological functions. These toxins are also promising lead compounds for developing treatments for many neurological diseases. In the current study, we purified a new scorpion toxin designated as BmK NSPK (Buthus martensii Karsch neurite-stimulating peptide targeting Kv channels) from the BmK venom. The primary structure was determined using Edman degradation. BmK NSPK directly inhibited outward K+ current without affecting sodium channel activities, depolarized membrane, and increased spontaneous calcium oscillation in spinal cord neurons (SCNs) at low nanomolar concentrations. BmK NSPK produced a nonmonotonic increase on the neurite extension that peaked at ~10 nM. Mechanistic studies demonstrated that BmK NSPK increased the release of nerve growth factor (NGF). The tyrosine kinases A (TrkA) receptor inhibitor, GW 441756, eliminated the BmK NSPK-induced neurite outgrowth. BmK NSPK also increased phosphorylation levels of protein kinase B (Akt) that is the downstream regulator of TrkA receptors. These data demonstrate that BmK NSPK is a new voltage-gated potassium (Kv) channel inhibitor that augments neurite extension via NGF/TrkA signaling pathway. Kv channels may represent molecular targets to modulate SCN development and regeneration and to develop the treatments for spinal cord injury.


2011 ◽  
Vol 7 ◽  
pp. 1744-8069-7-67 ◽  
Author(s):  
Michael E Hildebrand ◽  
Janette Mezeyova ◽  
Paula L Smith ◽  
Michael W Salter ◽  
Elizabeth Tringham ◽  
...  

2010 ◽  
Vol 26 (2) ◽  
pp. 117-125 ◽  
Author(s):  
Ping Yang ◽  
Zhen-Qiang Li ◽  
Lin Song ◽  
Yu-Qin Yin

2017 ◽  
Vol 95 (9) ◽  
pp. 653-661 ◽  
Author(s):  
C.D. Rand ◽  
G.E. Spencer ◽  
R.L. Carlone

Retinoic acid (RA), an active metabolite of vitamin A, is important for neural development and regeneration and can induce neurite outgrowth. It may also act as a guidance molecule by attracting neurite processes during outgrowth. In the African Clawed Frog (Xenopus laevis (Daudin, 1802)), RA has been shown to play an important role in the development of the anterior–posterior axis. However, whether RA can act as a trophic or tropic molecule on embryonic neurons of this species has not been determined. In this study, we investigated the effects of two retinoid isomers, all-trans retinoic acid (atRA) and 9-cis retinoic acid (9-cisRA), on cultured embryonic spinal cord neurons of X. laevis. Both isomers significantly enhanced neurite outgrowth compared with the vehicle control. In addition, atRA induced growth cone turning, which was blocked with a retinoic acid receptor (RAR) antagonist, selective for the β receptor subtype. Immunostaining also revealed RAR immunoreactivity in the neurites and growth cones of these cells. Interestingly, the 9-cisRA isomer also induced significant growth cone turning and this response was inhibited by a retinoid X receptor (RXR) pan-antagonist. Overall, we have provided evidence for both trophic and chemotropic actions of two naturally occurring retinoid isomers on Xenopus embryonic spinal cord neurons in culture.


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