Synergistic Inhibition of ERK1/2 and JNK, Not p38, Phosphorylation Ameliorates Neuronal Damages After Traumatic Brain Injury

Synergistic Inhibition of ERK1/2 and JNK, Not p38, Phosphorylation Ameliorates Neuronal Damages... Mitogen-activated protein (MAP) kinases are serine/threonine protein kinases that play a critical role in signal transduction and are activated by phosphorylation in response to a variety of pathophysiology stimuli. While MAP kinase signaling has a significant role in the pathophysiology of several neurodegenerative diseases, the precise function of activation of MAP kinase in traumatic brain injury (TBI) is unknown. Therefore, it is important to study the role of MAP kinase signaling in TBI-associated neurological ailments. In this study, using an in vitro stretch injury model in rat embryo neuronal cultures and the in vivo fluid percussion injury (FPI) model in rats, we explored the role of MAP kinase signaling in the mechanisms of cell death in TBI. Our study demonstrated that the stretch injury in vitro and FPI in vivo upregulated the phosphorylation of MAP kinase proteins ERK1/2 and JNK, but not p38. Using ERK1/2 inhibitor U0126, JNK inhibitor SP600125, and p38 inhibitor SB203580, we validated the role of MAP kinase proteins in the activation of NF-kB and caspase-3. By immunofluorescence and western blotting, further, we demonstrated the role of ERK1/2 and JNK phosphorylation in neurodegeneration by analyzing cell death proteins annexin V and Poly-ADP-Ribose-Polymerase p85. Interestingly, combined use http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Molecular Neurobiology Springer Journals

Synergistic Inhibition of ERK1/2 and JNK, Not p38, Phosphorylation Ameliorates Neuronal Damages After Traumatic Brain Injury

Loading next page...
 
/lp/springer_journal/synergistic-inhibition-of-erk1-2-and-jnk-not-p38-phosphorylation-mfefWqaw0D
Publisher
Springer Journals
Copyright
Copyright © 2018 by Springer Science+Business Media, LLC, part of Springer Nature
Subject
Biomedicine; Neurosciences; Neurobiology; Cell Biology; Neurology
ISSN
0893-7648
eISSN
1559-1182
D.O.I.
10.1007/s12035-018-1132-7
Publisher site
See Article on Publisher Site

Abstract

Mitogen-activated protein (MAP) kinases are serine/threonine protein kinases that play a critical role in signal transduction and are activated by phosphorylation in response to a variety of pathophysiology stimuli. While MAP kinase signaling has a significant role in the pathophysiology of several neurodegenerative diseases, the precise function of activation of MAP kinase in traumatic brain injury (TBI) is unknown. Therefore, it is important to study the role of MAP kinase signaling in TBI-associated neurological ailments. In this study, using an in vitro stretch injury model in rat embryo neuronal cultures and the in vivo fluid percussion injury (FPI) model in rats, we explored the role of MAP kinase signaling in the mechanisms of cell death in TBI. Our study demonstrated that the stretch injury in vitro and FPI in vivo upregulated the phosphorylation of MAP kinase proteins ERK1/2 and JNK, but not p38. Using ERK1/2 inhibitor U0126, JNK inhibitor SP600125, and p38 inhibitor SB203580, we validated the role of MAP kinase proteins in the activation of NF-kB and caspase-3. By immunofluorescence and western blotting, further, we demonstrated the role of ERK1/2 and JNK phosphorylation in neurodegeneration by analyzing cell death proteins annexin V and Poly-ADP-Ribose-Polymerase p85. Interestingly, combined use

Journal

Molecular NeurobiologySpringer Journals

Published: Jun 6, 2018

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off