Thymoquinone (Tq) protects necroptosis induced by autophagy/mitophagy-dependent oxidative stress in human bronchial epithelial cells exposed to cigarette smoke extract (CSE). 2020

Ayed A Dera, and Majed Al Fayi, and Hassan Otifi, and Mishari Alshyarba, and Mohammad Alfhili, and Prasanna Rajagopalan
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia.

Chronic obstructive pulmonary disease (COPD) is characterized by cigarette smoke-induced emphysema. Herein, we demonstrate protective effects of Thymoquinone (Tq), an active constituent from Nigella sativa, against cigarette smoke extract (CSE)-induced abnormalities in bronchial epithelial cells. Dose-dependent reduction in cell viability was observed in BEAS-2B cells when exposed to different CSE concentrations, which was significantly reversed by Tq evident by LDH release. Levels of SOD, CAT, GR , GSH, and mitochondrial membrane ATPases were significantly reduced upon CSE exposure, an event, again, antagonized in presence of Tq. Similarly, Tq treatment significantly blocked CSE-induced 4HNE elevations. Further, Tq-improved mitochondrial dysfunction caused by CSE and significantly decreased autophagy/mitophagy markers like LC3II and p-Drp. Tq also reduced necroptosis markers such as p-MLKL, RIP-1, and RIP-3, by stabilizing PINK-1 levels. In summary, Tq possesses protective properties against human bronchial epithelial cell autophagy/mitophagy-dependent necroptosis caused by CSE, which warrants considerable attention for further preclinical evaluations. PRACTICAL APPLICATIONS: This study demonstrates Thymoquinone (Tq), a natural plant extract to possess protective properties against human bronchial epithelial cell autophagy/mitophagy-dependent necroptosis caused by cigarette smoke extract. The demonstrated efficacy of Tq will throw light for further preclinical evaluation of this molecule in CSE-mediated complications. A detailed in vivo research is recommended.

UI MeSH Term Description Entries
D001980 Bronchi The larger air passages of the lungs arising from the terminal bifurcation of the TRACHEA. They include the largest two primary bronchi which branch out into secondary bronchi, and tertiary bronchi which extend into BRONCHIOLES and PULMONARY ALVEOLI. Primary Bronchi,Primary Bronchus,Secondary Bronchi,Secondary Bronchus,Tertiary Bronchi,Tertiary Bronchus,Bronchi, Primary,Bronchi, Secondary,Bronchi, Tertiary,Bronchus,Bronchus, Primary,Bronchus, Secondary,Bronchus, Tertiary
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004847 Epithelial Cells Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells. Adenomatous Epithelial Cells,Columnar Glandular Epithelial Cells,Cuboidal Glandular Epithelial Cells,Glandular Epithelial Cells,Squamous Cells,Squamous Epithelial Cells,Transitional Epithelial Cells,Adenomatous Epithelial Cell,Cell, Adenomatous Epithelial,Cell, Epithelial,Cell, Glandular Epithelial,Cell, Squamous,Cell, Squamous Epithelial,Cell, Transitional Epithelial,Cells, Adenomatous Epithelial,Cells, Epithelial,Cells, Glandular Epithelial,Cells, Squamous,Cells, Squamous Epithelial,Cells, Transitional Epithelial,Epithelial Cell,Epithelial Cell, Adenomatous,Epithelial Cell, Glandular,Epithelial Cell, Squamous,Epithelial Cell, Transitional,Epithelial Cells, Adenomatous,Epithelial Cells, Glandular,Epithelial Cells, Squamous,Epithelial Cells, Transitional,Glandular Epithelial Cell,Squamous Cell,Squamous Epithelial Cell,Transitional Epithelial Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000079302 Necroptosis A form of regulated cell death initiated by perturbations of extracellular or intracellular homeostasis that trigger a specific cell death pathway involving the activation of RIPK3 and MLKL (mixed lineage kinase domain like pseudokinase). Morphological changes include cytoplasmic and organellar swelling, rupture of the PLASMA MEMBRANE, and CHROMATIN CONDENSATION.
D001343 Autophagy The segregation and degradation of various cytoplasmic constituents via engulfment by MULTIVESICULAR BODIES; VACUOLES; or AUTOPHAGOSOMES and their digestion by LYSOSOMES. It plays an important role in BIOLOGICAL METAMORPHOSIS and in the removal of bone by OSTEOCLASTS. Defective autophagy is associated with various diseases, including NEURODEGENERATIVE DISEASES and cancer. Autophagocytosis,ER-Phagy,Lipophagy,Nucleophagy,Reticulophagy,Ribophagy,Autophagy, Cellular,Cellular Autophagy,ER Phagy
D012907 Smoking Willful or deliberate act of inhaling and exhaling SMOKE from burning substances or agents held by hand. Smoking Behaviors,Smoking Habit,Behavior, Smoking,Behaviors, Smoking,Habit, Smoking,Habits, Smoking,Smoking Behavior,Smoking Habits
D016227 Benzoquinones Benzene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups. 1,2-Benzoquinones,1,4-Benzoquinones,Benzodiones,2,5-Cyclohexadiene-1,4-Diones,o-Benzoquinones,p-Benzoquinones
D018384 Oxidative Stress A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). Anti-oxidative Stress,Antioxidative Stress,DNA Oxidative Damage,Nitro-Oxidative Stress,Oxidative Cleavage,Oxidative DNA Damage,Oxidative Damage,Oxidative Injury,Oxidative Nitrative Stress,Oxidative Stress Injury,Oxidative and Nitrosative Stress,Stress, Oxidative,Anti oxidative Stress,Anti-oxidative Stresses,Antioxidative Stresses,Cleavage, Oxidative,DNA Damage, Oxidative,DNA Oxidative Damages,Damage, DNA Oxidative,Damage, Oxidative,Damage, Oxidative DNA,Injury, Oxidative,Injury, Oxidative Stress,Nitrative Stress, Oxidative,Nitro Oxidative Stress,Nitro-Oxidative Stresses,Oxidative Cleavages,Oxidative DNA Damages,Oxidative Damage, DNA,Oxidative Damages,Oxidative Injuries,Oxidative Nitrative Stresses,Oxidative Stress Injuries,Oxidative Stresses,Stress Injury, Oxidative,Stress, Anti-oxidative,Stress, Antioxidative,Stress, Nitro-Oxidative,Stress, Oxidative Nitrative,Stresses, Nitro-Oxidative
D063306 Mitophagy Proteolytic breakdown of the MITOCHONDRIA via autophagy. Mitochondrial Degradation

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