Related Experiment Video

Updated: Aug 11, 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

Cadmium-induced apoptosis in rat kidney epithelial cells involves decrease in nuclear factor-kappa B activity

Jianxun Xie1, Zahir A Shaikh

  • 1Department of Biomedical and Pharmaceutical Sciences and Center for Molecular Toxicology, College of Pharmacy, University of Rhode Island, Kingston, Rhode Island 02881, USA.

Toxicological Sciences : an Official Journal of the Society of Toxicology
|February 16, 2006
PubMed

Insights

Cadmium exposure triggers apoptosis in kidney cells by suppressing nuclear factor-kappa B (NF-kappaB) activity, potentially through oxidative stress. Restoring NF-kappaB function protects cells from this damage.

Area of Science:

  • Toxicology
  • Cell Biology
  • Molecular Biology

Background:

  • Renal epithelial cells undergo apoptosis when exposed to toxic substances like cadmium (Cd).
  • Nuclear factor-kappa B (NF-kappaB) is a transcription factor known to regulate genes involved in apoptosis.
  • Understanding the role of NF-kappaB in cadmium-induced apoptosis is crucial for cellular protection strategies.

Purpose of the Study:

  • To investigate the involvement of the NF-kappaB transcription factor in cadmium-induced apoptosis of rat kidney proximal tubular epithelial cells (NRK-52E).
  • To elucidate the mechanisms by which cadmium affects NF-kappaB activity and its downstream targets.
  • To determine if oxidative stress mediates the suppression of NF-kappaB by cadmium.

Main Methods:

  • NRK-52E cells were exposed to varying concentrations of cadmium chloride (CdCl2).
  • NF-kappaB DNA-binding activity, IkappaB kinase alpha activity, and protein phosphorylation (IkappaB-alpha, NF-kappaB p65) were assessed.
  • Apoptosis was quantified using flow cytometry, and caspase activation and DNA fragmentation were measured.
  • Cells were pretreated with antioxidants or NF-kappaB inhibitors/activators to evaluate their effects.

Main Results:

  • Cadmium exposure decreased NF-kappaB DNA-binding activity and inhibited IkappaB kinase alpha in a dose- and time-dependent manner.
  • Cadmium reduced the phosphorylation of IkappaB-alpha and NF-kappaB p65, and decreased levels of NF-kappaB target genes (cIAP-1, cIAP-2).
  • Cadmium induced caspase activation, DNA fragmentation, and apoptosis, which were attenuated by antioxidants and NF-kappaB activation, but potentiated by NF-kappaB inhibition.

Conclusions:

  • Cadmium-induced apoptosis in renal epithelial cells involves the suppression of NF-kappaB activity.
  • Oxidative stress may play a role in mediating the inhibitory effects of cadmium on NF-kappaB.
  • Modulating NF-kappaB activity offers a potential therapeutic strategy against cadmium-induced kidney injury.

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

Antagonistic Effect of Jiawei Shengjiang San on a Rat Model of Diabetic Nephropathy: Related to EGFR/MAPK3/1 Signaling Pathway08:15

Antagonistic Effect of Jiawei Shengjiang San on a Rat Model of Diabetic Nephropathy: Related to EGFR/MAPK3/1 Signaling Pathway

Published on: May 10, 2024

Related Concept Videos

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...
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...
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...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

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...
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...