Reactive Oxygen Species (ROS)-related gene expression [Neurosurgery Wiki]

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====== Reactive Oxygen Species (ROS)-related gene expression ======

[[Reactive Oxygen Species (ROS)-related gene expression in glioma]]

[[Reactive Oxygen Species]] ([[ROS]])-related [[gene expression]] encompasses the [[transcriptional regulation]] of genes involved in the production, detoxification, and response to ROS, as well as the [[cellular signaling]] pathways they influence. ROS are key molecules in various physiological processes, such as [[cell signaling]], [[immune response]], and [[apoptosis]]. Dysregulation of ROS levels can lead to [[oxidative stress]], contributing to diseases like [[cancer]], [[neurodegeneration]], and cardiovascular disorders.

===== Genes Associated with ROS Production =====

Mitochondrial ROS Production:

[[MT-ND1]], [[MT-ND2]]: Encode components of Complex I in the electron transport chain, where superoxide is generated.

CYCS ([[Cytochrome C]]): Links the mitochondrial electron transport chain to ROS-induced apoptosis.

[[NADPH]] Oxidase Complex (NOX Family):

[[NOX1]], [[NOX2]], [[NOX4]], NOX5: Catalyze the production of superoxide from oxygen using NADPH.

DUOX1, DUOX2: Generate hydrogen peroxide and play roles in thyroid function and epithelial defense.

[[Xanthine Oxidase]] (XDH):

Converts hypoxanthine to xanthine, producing superoxide as a byproduct.

[[Cytochrome]] P450 Enzymes (CYPs):

Byproducts of these monooxygenases include ROS, particularly in drug metabolism.

Genes Associated with ROS Detoxification

Superoxide Dismutases (SODs):

SOD1 (cytosolic): Converts superoxide to hydrogen peroxide in the cytoplasm.

SOD2 (mitochondrial): Protects mitochondria from oxidative damage.

SOD3 (extracellular): Detoxifies superoxide in extracellular spaces.

[[Catalase]] (CAT):

Breaks down hydrogen peroxide into water and oxygen, preventing oxidative stress.

Glutathione Peroxidases (GPXs):

[[GPX1]], [[GPX4]]: Reduce hydrogen peroxide and lipid peroxides using glutathione.

Peroxiredoxins (PRDXs):

PRDX1-6: Detoxify peroxides and contribute to cellular redox signaling.

[[Thioredoxin]] (TXN) System:

TXN1, TXN2: Reduce oxidized proteins and ROS through electron donation.

Genes Regulating Cellular Responses to ROS

[[NRF2]] Pathway (NFE2L2):

Activates a broad antioxidant response, inducing genes like:

HMOX1 (heme oxygenase 1): Antioxidant and anti-inflammatory effects.

NQO1 (NAD(P)H quinone oxidoreductase 1): Detoxifies quinones and reduces ROS.

GCLC, GCLM: Catalyze glutathione biosynthesis.

Hypoxia-Inducible Factor (HIF-1α):

Regulates genes involved in the adaptation to oxidative stress under low oxygen conditions.

AP-1 (FOS, JUN):

Transcription factor complex that modulates gene expression in response to oxidative stress.

[[p53]] (TP53):

Activates genes involved in DNA repair, cell cycle arrest, and apoptosis in response to ROS-induced damage.

FOXO Family (FOXO1, FOXO3):

Induce antioxidant genes like CAT, SOD2, and others to mitigate ROS damage.

ATF4 (Activating Transcription Factor 4):

Regulates genes in response to oxidative and endoplasmic reticulum stress.

Disease Implications of ROS-Related Gene Dysregulation

Cancer:

Overexpression of [[NOX4]] promotes tumor growth by increasing ROS.

Downregulation of NRF2 or overactivation may lead to oxidative damage or chemoresistance.

Neurodegenerative Diseases:

SOD1 mutations are linked to amyotrophic lateral sclerosis (ALS).

Increased ROS contributes to mitochondrial dysfunction in Alzheimer's and Parkinson's disease.

Cardiovascular Diseases:

Overactive NOX2 and reduced SOD2 exacerbate oxidative damage in ischemia-reperfusion injury.

Diabetes:

Increased ROS in mitochondria and reduced detoxification by CAT and GPX1 lead to endothelial dysfunction.

Experimental Tools for ROS-Related Gene Expression

RT-qPCR: To quantify expression of ROS-related genes.

RNA-Seq: For a comprehensive analysis of gene expression changes in response to ROS.

ChIP-Seq: To study transcription factor binding (e.g., NRF2, p53) on ROS-related genes.

Western Blot: To measure protein levels of ROS detoxifying enzymes (e.g., SOD, catalase).
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