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Related Concept Videos

Nitric Oxide Signaling Pathway01:28

Nitric Oxide Signaling Pathway

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Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
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Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
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Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
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Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
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Calcium is not only the most abundant mineral in bone but also the most abundant mineral in the human body. Calcium ions are needed for bone mineralization, tooth health, heart rate regulation and strength of contraction, blood coagulation, the contraction of smooth and skeletal muscle cells, and the regulation of nerve impulse conduction. The average calcium level in the blood is about 10 mg/dL. When the body cannot maintain this level, a person will experience hypo or hypercalcemia.
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ROS Live Cell Imaging During Neuronal Development
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NOX4-derived ROS are neuroprotective by balancing intracellular calcium stores.

Lukas Gola1, Laura Bierhansl1, Júlia Csatári1

  • 1Department of Neurology with Institute of Translational Neurology, University Hospital Münster, 48149, Münster, Germany.

Cellular and Molecular Life Sciences : CMLS
|April 20, 2023
PubMed
Summary

NOX4, an enzyme producing reactive oxygen species (ROS), protects neurons from death by regulating calcium and ROS levels. This enzyme is neuroprotective against hyperexcitability, suggesting a role in preventing neurodegeneration.

Keywords:
Calcium signalingHyperexcitabilityMitochondriaNADPH oxidase-4 (NOX4)NeurodegenerationReactive oxygen species (ROS)

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Area of Science:

  • Neuroscience
  • Cellular Biology
  • Biochemistry

Background:

  • Neuronal hyperexcitability contributes to cell death and neurodegeneration.
  • Redox imbalance and increased reactive oxygen species (ROS) are implicated in neurological diseases.
  • NADPH oxidase 4 (NOX4) produces ROS and may regulate oxidative stress.

Purpose of the Study:

  • To investigate the role of NOX4 in neuronal firing and hyperexcitability.
  • To determine how NOX4 influences neural network function during hyperexcitability.
  • To explore NOX4's impact on oxidative stress, calcium homeostasis, and neuronal survival.

Main Methods:

  • Utilized an in vivo model of hyperexcitability.
  • Performed proteomic analysis to identify molecular changes.
  • Conducted cellular function analysis focusing on ROS, mitochondrial integrity, and calcium levels.

Main Results:

  • NOX4 demonstrated a neuroprotective effect.
  • NOX4 was found to regulate ROS and calcium homeostasis.
  • The enzyme prevented hyperexcitability-induced neuronal death.

Conclusions:

  • NOX4 plays a beneficial role in managing hyperexcitability.
  • NOX4 acts as a redox regulator, safeguarding against neuronal death.
  • NOX4 may be a significant factor in mitigating neurodegeneration.