Calpain inhibitors reduce the cornified cell envelope formation by inhibiting proteolytic processing of

Related Experiment Video

Updated: Oct 26, 2026

Mechanical Stimulation-induced Calcium Wave Propagation in Cell Monolayers: The Example of Bovine Corneal Endothelial Cells
10:46

Mechanical Stimulation-induced Calcium Wave Propagation in Cell Monolayers: The Example of Bovine Corneal Endothelial Cells

Published on: July 16, 2013

S Y Kim1, C D Bae

  • 1Laboratory of Skin Biology, NIAMS, NIH, Bethesda, MD 20892-2755, USA.

Experimental & Molecular Medicine
|January 23, 1999
PubMed

Insights

Calpain inhibitors significantly reduced cornified envelope formation in human keratinocytes, suggesting calpains activate TGase 1 for epidermal differentiation. This finding impacts understanding of skin barrier development.

Area of Science:

  • Biochemistry
  • Dermatology
  • Cell Biology

Background:

  • Calpains are calcium-activated cysteine proteases implicated in various biological processes.
  • Calpain activation is linked to conditions like cataract formation and neuronal degeneration.
  • Their role in epidermal differentiation and cornified envelope formation requires further elucidation.

Purpose of the Study:

  • To investigate the role of calpains in the formation of insoluble cornified envelopes (CE) during epidermal differentiation.
  • To determine if calpain inhibition affects TGase 1 activity, crucial for CE formation.

Main Methods:

  • Normal human epidermal keratinocytes (NHEK) were treated with calpain I inhibitor (N-acetyl-leucyl-leucyl-norleucinal).
  • Cells were cultured under calcium-induced differentiation conditions with varying inhibitor concentrations.
  • Insoluble CE formation and TGase activity were measured over time.

Main Results:

  • Calpain I inhibition (50 microM) reduced insoluble CE formation by approximately 90% by day 9.
  • TGase activity was blocked by 90% within 72 hours with 0.5 mM calpain inhibitor treatment.
  • Serine and thiol protease inhibitors showed minimal effect on CE formation and TGase activity.

Conclusions:

  • Cysteine protease calpains are likely responsible for activating TGase 1.
  • This activation is essential for the complete formation of insoluble CE during epidermal differentiation.
  • Calpains represent a potential target for modulating skin barrier function.

Related Concept Videos

Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult body.
A...
Inhibitors of Gram-positive Cell Wall Synthesis01:23

Inhibitors of Gram-positive Cell Wall Synthesis

Bacterial cell walls are typically rigid structures composed mainly of peptidoglycan, a mesh-like polymer that provides mechanical strength and maintains cell shape. The synthesis of peptidoglycan is a crucial process in bacterial growth and serves as a primary target for many antibiotics.Mechanism of Action of Beta-Lactam AntibioticsBeta-lactam antibiotics, such as penicillin, inhibit peptidoglycan synthesis in actively growing cells. These antibiotics share a characteristic four-membered...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Tight Junctions01:29

Tight Junctions

Tight junctions are molecular seals between cells that prevent the leaking of fluids, ions, and other small solutes across cavities and compartments in multicellular organisms. They are mainly composed of claudin and occludin transmembrane proteins, and other proteins such as tricellulin and JAM (junctional adhesion molecule). All these proteins are 4-pass transmembrane proteins, except JAM, which is a single-pass transmembrane protein belonging to the immunoglobulin superfamily. The...
Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...