Related Experiment Video

Updated: Aug 24, 2026

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen
19:44

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen

Published on: May 30, 2012

Insulin-like growth factor-I regulates glucose-induced mitochondrial depolarization and apoptosis in human

G M Leinninger1, J W Russell, C M van Golen

  • 1Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.

Cell Death and Differentiation
|April 24, 2004
PubMed

Insights

High glucose levels trigger apoptosis in neuroblastoma cells by affecting mitochondria and caspases. Insulin-like growth factor I (IGF-I) protects these cells from this programmed cell death.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Oncology

Background:

  • Neuroblastoma, a pediatric nervous system tumor, exhibits chemoresistance due to altered apoptotic pathways.
  • Insulin-like growth factor (IGF) system components are highly expressed in neuroblastoma, promoting cell survival by inhibiting apoptosis.

Purpose of the Study:

  • To investigate the role of IGF-I in regulating apoptosis at the mitochondrial level in neuroblastoma cells.
  • To elucidate the mechanisms by which elevated glucose affects apoptosis in neuroblastoma.

Main Methods:

  • Mitochondrial membrane potential (Delta Psi(M)) and mitochondrial membrane depolarization (MMD) were measured.
  • Caspase activation (caspase-3 and caspase-9), uncoupling protein 3 (UCP3) expression, and Bcl-2 levels were assessed.
  • The effects of Bongkrekic acid and caspase-9 inhibition on glucose-induced apoptosis were evaluated.

Main Results:

  • Elevated extracellular glucose induced rapid mitochondrial enlargement, increased Delta Psi(M), followed by MMD, UCP3 downregulation, caspase-3 activation, and decreased Bcl-2.
  • MMD inhibition prevented high-glucose-induced UCP3 loss and apoptosis.
  • Glucose exposure triggered caspase-9 cleavage within 30 minutes, and caspase-9 inhibition blocked glucose-mediated apoptosis.
  • IGF-I effectively prevented caspase activation and the mitochondrial events leading to apoptosis.

Conclusions:

  • Elevated glucose initiates apoptosis in neuroblastoma cells via early caspase activation and subsequent mitochondrial changes.
  • IGF-I confers protection by inhibiting downstream caspase activation, preserving mitochondrial membrane potential, and regulating Bcl proteins, thereby preventing apoptosis.

More Related Videos

Subcellular Fractionation for ERK Activation Upon Mitochondrial-derived Peptide Treatment07:55

Subcellular Fractionation for ERK Activation Upon Mitochondrial-derived Peptide Treatment

Published on: September 25, 2017

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity04:20

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity

Published on: February 9, 2024

Related Concept Videos

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...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
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...