Related Experiment Video

Updated: May 18, 2026

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
07:42

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c

Published on: June 29, 2011

NOX1/NADPH oxidase is involved in endotoxin-induced cardiomyocyte apoptosis

Kuniharu Matsuno1, Kazumi Iwata, Misaki Matsumoto

  • 1Department of Pharmacology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Free Radical Biology & Medicine
|September 18, 2012
PubMed

Insights

Reactive oxygen species (ROS) from NOX1/NADPH oxidase drive septic heart damage and mortality. Mice lacking NOX1 show improved cardiac function and survival during sepsis, highlighting NOX1

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Inflammation Research

Background:

  • The role of NOX1/NADPH oxidase in cardiac function during sepsis remains largely unexplored due to its typically low expression.
  • Systemic inflammation, such as sepsis, can lead to significant cardiac dysfunction and increased mortality.
  • Reactive oxygen species (ROS) are implicated in various pathological processes, including sepsis-induced organ damage.

Purpose of the Study:

  • To investigate the functional significance of NOX1/NADPH oxidase in the heart during sepsis.
  • To elucidate the molecular mechanisms by which NOX1 contributes to septic cardiomyopathy.
  • To assess the therapeutic potential of targeting NOX1 in sepsis.

Main Methods:

  • Utilized Nox1 gene-deficient (Nox1(-/Y)) and wild-type (Nox1(+/Y)) mice.
  • Induced sepsis using lipopolysaccharide (LPS) administration and cecal ligation and puncture (CLP) surgery.
  • Assessed cardiac function, survival rates, cardiomyocyte apoptosis, caspase-3 activation, and Akt signaling pathways, including phosphorylation and interaction with protein phosphatase 2A (PP2A).

Main Results:

  • Sepsis induced a marked elevation of NOX1 mRNA and ROS production in cardiac tissue.
  • Nox1(-/Y) mice exhibited significantly improved cardiac function and survival compared to wild-type mice following LPS challenge.
  • LPS-induced cardiomyocyte apoptosis, caspase-3 activation, and Akt dephosphorylation were significantly attenuated in Nox1(-/Y) mice.
  • Increased oxidation of Akt and enhanced Akt-PP2A interaction in response to LPS were observed in wild-type but not Nox1(-/Y) mice.

Conclusions:

  • ROS derived from NOX1/NADPH oxidase play a critical role in endotoxin-induced cardiomyocyte apoptosis and cardiac dysfunction during sepsis.
  • NOX1 contributes to sepsis-induced cardiac injury by promoting Akt oxidation and subsequent dephosphorylation via PP2A.
  • Up-regulation of NOX1 during systemic inflammation may be a significant risk factor for mortality in sepsis.

Related Concept Videos

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,...
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...
Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...
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...
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
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...