Related Experiment Video

Updated: Jun 27, 2026

Assaying Protein Kinase Activity with Radiolabeled ATP
08:05

Assaying Protein Kinase Activity with Radiolabeled ATP

Published on: May 26, 2017

Activating deltaPKC antagonizes the protective effect of ERK1/2 inhibition against stroke in rats

Dora Castañeda1, Heng Zhao, Daria Mochly-Rosen

  • 1Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.

Brain Research
|December 10, 2008
PubMed

Insights

Inhibiting both the MEK/ERK cascade and the deltaPKC pathway reduces cerebral ischemic damage. Targeting these pathways independently or in combination offers therapeutic potential for stroke.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pathology

Background:

  • Cerebral ischemic damage involves the MEK/ERK cascade and the pro-apoptotic deltaPKC pathway.
  • Understanding the interplay between these pathways is crucial for developing effective stroke treatments.

Purpose of the Study:

  • To investigate the relationship between the MEK/ERK and deltaPKC pathways in a rat model of focal ischemia.
  • To evaluate the therapeutic potential of modulating these pathways individually and in combination.

Main Methods:

  • Rats with focal ischemia were treated with MEK/ERK inhibitor (U0126) and/or deltaPKC inhibitor (deltaV1-1) or activator (psi deltaRACK).
  • Levels of phosphorylated ERK1/2 (P-ERK1/2) and infarct size were measured.
  • Inhibitors/activators were administered at different time points relative to ischemia onset and reperfusion.

Main Results:

  • U0126 at ischemia onset reduced P-ERK1/2 and infarct size, but not when given at reperfusion.
  • deltaV1-1 did not significantly alter P-ERK1/2 levels, while psi deltaRACK reduced them.
  • Combined inhibition of both pathways yielded greater infarct reduction than either alone.

Conclusions:

  • The MEK/ERK and deltaPKC pathways likely act independently in mediating ischemic damage.
  • Simultaneous inhibition of both pathways provides enhanced neuroprotection in focal ischemia.
  • Targeting both pathways represents a promising therapeutic strategy for stroke treatment.

More Related Videos

Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting10:08

Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting

Published on: December 9, 2022

Related Concept Videos

MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...