Related Experiment Video

Updated: Jul 2, 2026

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation
06:12

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation

Published on: May 3, 2024

hMTH1 depletion promotes oxidative-stress-induced apoptosis through a Noxa- and caspase-3/7-mediated signaling

Cha-Kyung Youn1, Jae Yeoul Jun, Jin-Won Hyun

  • 1DNA Repair Research Center, Chosun University, 375 Seosuk-dong, Gwangju, Republic of Korea.

DNA Repair
|August 19, 2008
PubMed

Insights

Human NUDT1 (hMTH1) protects against oxidative stress-induced apoptosis by preventing DNA damage. Suppressing hMTH1 increases cell death via Noxa and caspase pathways, highlighting its role in cell survival.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Oxidative stress generates DNA damage, such as 8-oxo-dGTP, linked to apoptosis and mutagenesis.
  • The precise mechanism of human NUDT1 (hMTH1) in preventing oxidative-stress-induced cell death remains unclear.
  • hMTH1's role in DNA damage response and cell survival requires further elucidation.

Purpose of the Study:

  • To investigate the mechanism of hMTH1 in regulating DNA-damage-induced apoptosis.
  • To determine the role of hMTH1 in cellular response to hydrogen peroxide (H2O2)-induced oxidative stress.
  • To identify signaling pathways involved in hMTH1-mediated protection against DNA damage.

Main Methods:

  • Utilized small interfering RNA (siRNA) to knockdown hMTH1 expression in p53-proficient (GM00637, H460) and p53-null (H1299) cells.
  • Exposed cells to hydrogen peroxide (H2O2) to induce oxidative stress and measured apoptotic cell death.
  • Assessed caspase-3/7 activity, cleaved caspase-8, Noxa expression, and gamma-H2AX formation.

Main Results:

  • hMTH1 knockdown significantly increased H2O2-induced apoptosis in p53-proficient cells, but not in p53-null cells.
  • hMTH1-deficient cells exhibited elevated caspase-3/7 activity, cleaved caspase-8, Noxa, and gamma-H2AX after H2O2 exposure.
  • Inhibition of caspases or Noxa, and p53 knockdown, suppressed H2O2-induced cell death.
  • Long-term cultured hMTH1-suppressed cells showed increased sensitivity to H2O2-induced cell death, Noxa, and gamma-H2AX.

Conclusions:

  • hMTH1 is crucial for protecting cells against oxidative-stress-induced apoptosis.
  • The protective mechanism involves a pathway mediated by Noxa and caspase-3/7 signaling.
  • hMTH1 confers a survival advantage by inhibiting oxidative-stress-induced DNA damage.

More Related Videos

Use of a Caspase Multiplexing Assay to Determine Apoptosis in a Hypothalamic Cell Model08:27

Use of a Caspase Multiplexing Assay to Determine Apoptosis in a Hypothalamic Cell Model

Published on: April 16, 2014

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c07:42

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c

Published on: June 29, 2011

Related Concept Videos

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...
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...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
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.
Cellular Injury IV: Necrosis01:16

Cellular Injury IV: Necrosis

Necrosis is a form of irreversible cell death caused by severe injury such as ischemia, toxins, or trauma. Unlike programmed cell death, it is an uncontrolled, pathological process that typically provokes inflammation in surrounding tissues.Pathophysiologic ChangesNecrosis begins when cells sustain critical damage, leading to swelling of organelles, particularly mitochondria, and rapid ATP depletion. As energy levels decline, membrane ion pumps fail, leading to calcium influx and eventually,...
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...