Related Experiment Video

Updated: Aug 25, 2026

Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes
08:49

Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes

Published on: March 14, 2021

Phospholipase D in cellular senescence

M E Venable1, L M Obeid

  • 1Biology Department, Appalachian State University, P.O. Box 32027, Boone, NC 28608-2027, USA. venableme@appstate.edu

Biochimica Et Biophysica Acta
|July 30, 1999
PubMed

Insights

Cellular senescence, a hallmark of aging, involves defective early mitotic signals like the Phospholipase D (PLD)/Protein Kinase C (PKC) pathway. Elevated ceramide levels inhibit PLD activation, driving senescence.

Area of Science:

  • Cellular and Molecular Biology
  • Gerontology
  • Biochemistry

Background:

  • Cellular senescence is a key process in organismal aging, characterized by distinct morphological and molecular changes.
  • Key features include growth arrest, altered gene expression (e.g., p21, p16), and defective early mitotic signaling pathways.
  • The Phospholipase D (PLD)/Protein Kinase C (PKC) pathway is crucial for cell proliferation (mitogenesis).

Purpose of the Study:

  • To investigate the molecular mechanisms underlying the defect in the PLD/PKC pathway during cellular senescence.
  • To identify the role of ceramide in the pathogenesis of cellular senescence.

Main Methods:

  • Analysis of gene and protein expression in senescent cells.
  • Investigation of PLD and PKC pathway activation.
  • Experimental manipulation of ceramide levels in young and senescent cells.

Main Results:

  • Cellular senescence is associated with a defective PLD/PKC signaling pathway.
  • Elevated cellular ceramide levels were identified as a cause of PLD activation inhibition.
  • Neutral sphingomyelinase activation appears to be responsible for increased ceramide.
  • Ceramide inhibits PLD activation through multiple mechanisms, including interference with Rho signaling, membrane translocation, and gene expression.
  • Exogenous ceramide addition to young cells induced typical senescence phenotypes.

Conclusions:

  • Elevated ceramide, resulting from neutral sphingomyelinase activation, is a critical mediator of cellular senescence by inhibiting the PLD/PKC pathway.
  • Targeting ceramide metabolism or PLD/PKC signaling may offer therapeutic strategies for age-related conditions.

More Related Videos

A Liposome Membrane Permeability Assay for Investigating the Effects of Phosphatidylinositol Phosphate Groups on Membranotropic Action of Venom PLA210:31

A Liposome Membrane Permeability Assay for Investigating the Effects of Phosphatidylinositol Phosphate Groups on Membranotropic Action of Venom PLA2

Published on: September 26, 2025

Senescence Detection Using Reflected Light in Adipose Stromal Vascular Fraction10:08

Senescence Detection Using Reflected Light in Adipose Stromal Vascular Fraction

Published on: June 5, 2026

Related Concept Videos

Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
Synthesis of Phosphatidylcholine in the ER Membrane01:27

Synthesis of Phosphatidylcholine in the ER Membrane

The ER synthesizes lipids for building cell membranes and performing cellular functions such as energy storage and signaling. The lipid synthesis machinery embedded in the ER membrane primarily collects all reactants from the cytosol. Following synthesis, the secretory pathway and the ER contact sites distribute these lipids to other cellular organelles. Additionally, the energy-rich triacylglycerides are transported from the ER via lipid droplets.
The major components of all eukaryotic cell...
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
Cellular Injury IlI: Cellular Death01:11

Cellular Injury IlI: Cellular Death

Cell death is the irreversible loss of cellular structure and function, representing the final stage of severe injury. It plays a key role in both normal physiology and disease.Types of Cell DeathThe two main types are necrosis and apoptosis, though others like necroptosis and pyroptosis also exist.Necrosis:Necrosis is an unregulated form of cell death caused by severe injury such as trauma, toxins, or ischemia. It is characterized by cell swelling, membrane loss, rupture, and leakage of...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...