Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

3.8K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.8K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

7.4K
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...
7.4K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

5.8K
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...
5.8K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

6.1K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.1K
Abnormal Proliferation02:23

Abnormal Proliferation

5.3K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.3K
Negative Regulator Molecules01:23

Negative Regulator Molecules

38.6K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
38.6K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Overcoming Biological Barriers and Drug Resistance Through Next-Generation Nanotherapeutic Delivery in Gastric Cancer.

Cells·2026
Same author

Modern Polycystic Ovary Syndrome (PCOS) Management: Intelligent Drug Delivery and Metabolic Reprogramming for Ovarian Restoration and Fertility Optimization.

Biomolecules·2026
Same author

Autophagy-Circulating Tumor DNA Axis in Molecular Cancer Research: Emerging Mechanisms, Therapeutic Targeting, and Translational Opportunities.

International journal of molecular sciences·2026
Same author

Molecular Characterization of Ovarian Endometriosis in Saudi Arabian Women: Insights into Inflammatory, Autophagic, and Epigenetic Dysregulation.

International journal of molecular sciences·2026
Same author

Targeting AMPK Networks for Male Reproductive Health: Mechanisms and Emerging Therapies.

Cells·2026
Same author

Integration of phytochemical profiling and pharmacological assessment of Eucalyptus salubris seeds: a promising natural anti-inflammatory agent.

Inflammopharmacology·2026

Related Experiment Video

Updated: Feb 24, 2026

Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions
09:17

Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions

Published on: August 2, 2018

18.8K

Selective HIF-1 Regulation under Nonhypoxic Conditions by the p42/p44 MAP Kinase Inhibitor PD184161.

Maroua Jalouli1, Sophie Mokas1, Catherine A Turgeon1

  • 1Centre de recherche du CHU de Québec, Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Québec City, Québec, Canada.

Molecular Pharmacology
|August 18, 2017
PubMed
Summary
This summary is machine-generated.

The MEK1/2 inhibitor PD184161 blocks nonhypoxic activation of Hypoxia-Inducible Factor-1 (HIF-1) in vascular smooth muscle cells. It reduces mitochondrial ROS and increases ascorbate, impacting HIF-1α stability independently of MAPK signaling.

More Related Videos

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
08:34

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis

Published on: June 3, 2016

15.8K
Induction and Testing of Hypoxia in Cell Culture
07:01

Induction and Testing of Hypoxia in Cell Culture

Published on: August 12, 2011

86.4K

Related Experiment Videos

Last Updated: Feb 24, 2026

Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions
09:17

Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions

Published on: August 2, 2018

18.8K
Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
08:34

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis

Published on: June 3, 2016

15.8K
Induction and Testing of Hypoxia in Cell Culture
07:01

Induction and Testing of Hypoxia in Cell Culture

Published on: August 12, 2011

86.4K

Area of Science:

  • Cellular and Molecular Biology
  • Physiology
  • Biochemistry

Background:

  • Hypoxia-inducible factor-1 (HIF-1) regulates cellular adaptation to low oxygen.
  • Nonhypoxic stimuli, including hormones like angiotensin II (AngII), also regulate HIF-1 in vascular smooth muscle cells (VSMC).
  • AngII activates HIF-1 transcription via signaling pathways, including p42/p44 mitogen-activated protein kinase (MAPK).

Purpose of the Study:

  • To investigate the role of MEK1/2 inhibitor PD184161 in AngII-mediated HIF-1 activation in VSMC.
  • To determine the mechanism by which PD184161 affects HIF-1α protein induction and stability.
  • To explore the impact of PD184161 on mitochondrial reactive oxygen species (mtROS) and cellular energy levels.

Main Methods:

  • Dose-dependent treatment of VSMC with PD184161 and hypoxia (1% O2).
  • Assessment of HIF-1α protein induction and stability using proteasome inhibitor MG132.
  • Analysis of HIF-1α binding to von Hippel-Lindau tumor suppressor protein (VHL).
  • Measurement of mitochondrial ROS (mtROS) production, cellular ATP levels, and ascorbate availability.

Main Results:

  • PD184161 blocked AngII-driven HIF-1α protein induction in a dose-dependent manner, specifically under nonhypoxic conditions.
  • Unlike PD98059, PD184161's effect on HIF-1α induction was independent of p42/p44 MAPK activation.
  • PD184161 treatment led to increased HIF-1α binding to VHL, suggesting enhanced hydroxylation.
  • PD184161 inhibited mtROS production and cellular ATP levels, while increasing ascorbate availability in AngII-treated VSMC.

Conclusions:

  • PD184161 acts as an HIF-1 inhibitor in VSMC under nonhypoxic, AngII-stimulated conditions.
  • The mechanism involves blocking mtROS generation, re-establishing ascorbate levels, increasing VHL binding, and decreasing HIF-1α stability, independent of MAPK.
  • This study reveals a novel role for PD184161 in regulating HIF-1α stability via non-MAPK pathways in VSMC.