Related Experiment Video

Updated: Jan 20, 2026

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays
13:22

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays

Published on: October 23, 2019

8.2K

A specific small-molecule inhibitor of protein kinase CδI activity improves metabolic dysfunction in human adipocytes

Robert Sparks1, Ashley Lui2, Deena Bader3

  • 1Department of Biochemistry, University of Illinois, Urbana-Champaign, Illinois 61801.

The Journal of Biological Chemistry
|August 16, 2019
PubMed

Insights

Obesity causes inflammation and apoptosis via Protein Kinase C delta (PKCδI). A new inhibitor, NP627, blocks PKCδI activation, reducing inflammation and improving metabolism in obese adipocytes.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Metabolic Disease Research

Background:

  • Obesity is linked to severe metabolic disorders and inflammation.
  • Protein Kinase C delta (PKCδI) activation and release of its catalytic domain contribute to inflammation and apoptosis in adipocytes.
  • Increased PKCδI activation and pro-inflammatory cytokine expression are observed in adipocytes from obese individuals.

Purpose of the Study:

  • To identify and characterize a novel inhibitor of PKCδI.
  • To investigate the role of PKCδI in obesity-associated inflammation and metabolic dysfunction.
  • To evaluate the therapeutic potential of NP627 in managing obesity-related complications.

Main Methods:

  • Computational screening using Schrödinger software and molecular dynamics simulations to identify PKCδI inhibitors.
  • Surface Plasmon Resonance (SPR) for characterizing the binding affinity and specificity of NP627 to PKCδI.
  • In vitro kinase assays to confirm NP627's inhibitory activity against PKCδI.
  • Treatment of adipocytes from obese individuals with NP627 to assess its effects on inflammation, apoptosis, and mitochondrial metabolism.

Main Results:

  • NP627 was identified as a high-affinity and specific small-molecule inhibitor of PKCδI.
  • NP627 disrupts the binding of caspase-3 to PKCδI and inhibits PKCδI kinase activity.
  • NP627 treatment significantly reduced PKCδI catalytic fragment release, inflammation, and apoptosis in adipocytes from obese individuals.
  • NP627 treatment led to significant improvements in mitochondrial metabolism in obese adipocytes.

Conclusions:

  • PKCδI is a key mediator of inflammation and apoptosis in obesity-associated metabolic diseases.
  • NP627 is a promising therapeutic agent for targeting PKCδI to manage obesity-related chronic inflammatory conditions.
  • NP627 can be utilized to further elucidate the role of caspase-3-mediated kinase activation in biological systems.
Keywords:
NP627PKCadipocyteadipose tissueadipose tissue metabolismapoptosisinflammationmetabolic diseasemetabolic disorderobesity

More Related Videos

An Adipocyte Cell Culture Model to Study the Impact of Protein and Micro-RNA Modulation on Adipocyte Function09:20

An Adipocyte Cell Culture Model to Study the Impact of Protein and Micro-RNA Modulation on Adipocyte Function

Published on: May 4, 2021

4.2K
Protein Kinase C-delta Inhibitor Peptide Formulation using Gold Nanoparticles06:06

Protein Kinase C-delta Inhibitor Peptide Formulation using Gold Nanoparticles

Published on: March 9, 2019

5.8K

Related Concept Videos

Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
15.0K
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

4.4K
Pharmacokinetics in Obese Patients: Drug Metabolism and Excretion01:20

Pharmacokinetics in Obese Patients: Drug Metabolism and Excretion

Drug metabolism, a critical process in the liver, involves two primary phases: Phase I reactions and Phase II conjugation. Obesity introduces significant alterations in this metabolic process, primarily due to fatty infiltration of the liver, leading to conditions such as nonalcoholic fatty liver disease (NAFLD). This condition can modify the activities of both Phase I and II enzymes, impacting how drugs are metabolized in obese patients.Phase I metabolism sees variable effects across...
169
What is Metabolism?00:52

What is Metabolism?

Overview
131.2K
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
10.9K
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,...
8.3K