Related Experiment Video

Updated: Aug 25, 2026

Evaluation of Caspase Activation to Assess Innate Immune Cell Death
10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

Contribution of caveolin-1 alpha and Akt to TNF-alpha-induced cell death

Koh Ono1, Yoshitaka Iwanaga, Madoka Hirayama

  • 1Division of Translational Research, Kyoto Medical Center, National Hospital Organization, Kyoto 612-8555, Japan. kohono@kuhp.kyoto-u.ac.jp

American Journal of Physiology. Lung Cellular and Molecular Physiology
|March 17, 2004
PubMed

Insights

Caveolin-1 alpha is essential for tumor necrosis factor-alpha (TNF-alpha)-induced cell death in L929 cells. Its presence sensitizes cells to TNF-alpha via PI3K/Akt signaling, impacting apoptosis resistance.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Apoptosis Research

Background:

  • Tumor necrosis factor-alpha (TNF-alpha) is a key cytokine involved in inflammation and apoptosis.
  • Caveolins are structural proteins of caveolae, involved in various cellular signaling pathways.
  • Understanding the role of caveolins in cytokine-induced cell death is crucial for developing therapeutic strategies.

Purpose of the Study:

  • To investigate the role of caveolin-1 alpha in TNF-alpha-induced cell death.
  • To identify the signaling pathways mediating caveolin-1 alpha's effect on TNF-alpha sensitivity.
  • To explore the potential of targeting caveolin-1 alpha for modulating apoptosis.

Main Methods:

  • Retrovirus insertion-mediated random mutagenesis to generate TNF-alpha-resistant L929 cell lines.
  • Ectopic reconstitution of caveolin-1 alpha/beta expression in deficient cells.
  • Stable transfection of HepG2 cells (lacking endogenous caveolins) with caveolin-1 alpha/beta.
  • Treatment with TNF-alpha, H2O2, staurosporine, lonidamine, and PI3K inhibitors (LY-294002, wortmannin).

Main Results:

  • Caveolin-1 alpha deficiency confers resistance to TNF-alpha-induced cell death in L929 cells.
  • Restoration of caveolin-1 alpha/beta expression re-sensitizes cells to TNF-alpha.
  • Caveolin-1 alpha expression in HepG2 cells increases sensitivity to TNF-alpha.
  • Activation of the PI3K/Akt pathway is critical for caveolin-1 alpha-mediated sensitization to TNF-alpha.

Conclusions:

  • Caveolin-1 alpha plays a critical role in sensitizing cells to TNF-alpha-induced apoptosis.
  • The sensitization mechanism involves the activation of the PI3K/Akt signaling pathway.
  • Caveolin-1 alpha acts as a key regulator of TNF-alpha sensitivity, offering potential therapeutic targets.

More Related Videos

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes15:43

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

Published on: January 7, 2013

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

Related Concept Videos

The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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.
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...