Related Experiment Video

Updated: Aug 29, 2026

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

Mitogen-activated protein kinase/extracellular signal-regulated kinase attenuates 3-hydroxykynurenine-induced

Hyun Jung Lee1, Jae-Hyung Bach, Hee-Sun Chae

  • 1Department of Anatomy, College of Medicine, Chung-Ang University, Seoul, South Korea.

Journal of Neurochemistry
|January 15, 2004
PubMed

Insights

3-Hydroxykynurenine (3-HK) causes brain cell death. Extracellular signal-regulated kinase (ERK) activation protects neurons by maintaining mitochondrial function and regulating caspase activity during cellular stress.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Cell Biology

Background:

  • 3-Hydroxykynurenine (3-HK), a tryptophan metabolite, exhibits neurotoxicity.
  • The precise molecular mechanisms underlying 3-HK neurotoxicity remain unclear.

Purpose of the Study:

  • To investigate the role of MAPK/extracellular signal-regulated kinase (ERK) in 3-HK-induced neuronal cell damage.
  • To elucidate the protective mechanisms of ERK in neuronal cells under stress.

Main Methods:

  • Neuronal cell cultures were treated with 3-HK.
  • ERK activation was assessed via phosphorylation.
  • Mitochondrial function was evaluated by membrane potential and cytochrome c release.
  • Caspase activation was measured.
  • ERK inhibition was achieved using PD98059.

Main Results:

  • 3-HK induced apoptotic neuronal cell death.
  • ERK phosphorylation was observed during 3-HK-induced cell death.
  • Inhibition of ERK exacerbated cell death, mitochondrial dysfunction, and caspase activation.
  • 3-HK treatment led to mitochondrial membrane potential collapse and cytochrome c release.

Conclusions:

  • ERK activation plays a crucial protective role against 3-HK-induced neurotoxicity.
  • ERK safeguards neuronal cells by preserving mitochondrial integrity and modulating caspase activity.
  • Targeting ERK pathways may offer therapeutic strategies for neurodegenerative conditions involving 3-HK.

More Related Videos

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Related Concept Videos

MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
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...
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...
Enzyme-linked Receptors01:13

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...