Aspirin eugenol ester ameliorates paraquat-induced oxidative damage through ROS/p38-MAPK-mediated mitochondrial apoptosis pathway

Oxidative stress plays an important role in the pathogenesis of liver diseases. N-Acetyl-serotonin (NAS) has been reported to protect against oxidative damage, though the mechanisms by which NAS protects hepatocytes from oxidative stress remain unknown. To determine whether pretreatment with NAS could reduce hydrogen peroxide- (H2O2-) induced oxidative stress in HepG2 cells by inhibiting the mitochondrial apoptosis pathway, we investigated the H2O2-induced oxidative damage to HepG2 cells with or without NAS using MTT, Hoechst 33342, rhodamine 123, Terminal dUTP Nick End Labeling Assay (TUNEL), dihydrodichlorofluorescein (H2DCF), Annexin V and propidium iodide (PI) double staining, immunocytochemistry, and western blot. H2O2produced dramatic injuries in HepG2 cells, represented by classical morphological changes of apoptosis, increased levels of malondialdehyde (MDA) and intracellular reactive oxygen species (ROS), decreased activity of superoxide dismutase (SOD), and increased activities of caspase-9 and caspase-3, release of cytochrome c (Cyt-C) and apoptosis-inducing factor (AIF) from mitochondria, and loss of membrane potential (ΔΨm). NAS significantly inhibited H2O2-induced changes, indicating that it protected against H2O2-induced oxidative damage by reducing MDA levels and increasing SOD activity and that it protected the HepG2 cells from apoptosis through regulating the mitochondrial apoptosis pathway, involving inhibition of mitochondrial hyperpolarization, release of mitochondrial apoptogenic factors, and caspase activity.

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6-Hydroxydopamine activates the mitochondrial apoptosis pathway through p38 MAPK-mediated, p53-independent activation of Bax and PUMA

Journal of Neurochemistry ◽

10.1111/j.1471-4159.2007.05115.x ◽

2007 ◽

Vol 104 (6) ◽

pp. 1599-1612 ◽

Cited By ~ 92

Author(s):

Maria Gomez-Lazaro ◽

Maria F. Galindo ◽

Caoimhín G. Concannon ◽

Miguel F. Segura ◽

Francisco J. Fernandez-Gomez ◽

...

Keyword(s):

P38 Mapk ◽

Mitochondrial Apoptosis ◽

Apoptosis Pathway ◽

Mitochondrial Apoptosis Pathway ◽

6 Hydroxydopamine

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1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) Urea Exerts Neuro-Protective Effects Against Ischemic Injury via Suppressing JNK/p38 MAPK-Mediated Mitochondrial Apoptosis Pathway

Journal of Stroke and Cerebrovascular Diseases ◽

10.1016/j.jstrokecerebrovasdis.2021.105957 ◽

2021 ◽

Vol 30 (9) ◽

pp. 105957

Author(s):

Xingyang Yi ◽

Daofeng Fan ◽

Tong Yi ◽

Hong Chen ◽

Ting Qing ◽

...

Keyword(s):

P38 Mapk ◽

Ischemic Injury ◽

Protective Effects ◽

Mitochondrial Apoptosis ◽

Apoptosis Pathway ◽

Mitochondrial Apoptosis Pathway

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Melatonin Protects Goat Spermatogonial Stem Cells against Oxidative Damage during Cryopreservation by Improving Antioxidant Capacity and Inhibiting Mitochondrial Apoptosis Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/5954635 ◽

2020 ◽

Vol 2020 ◽

pp. 1-16

Author(s):

Tian-Yu Feng ◽

Qian Li ◽

Fa Ren ◽

Hua-Ming Xi ◽

Dong-Liang Lv ◽

...

Keyword(s):

Stem Cells ◽

Oxidative Damage ◽

Antioxidant Capacity ◽

Adult Stem Cells ◽

Spermatogonial Stem Cells ◽

Dairy Goat ◽

Protective Mechanism ◽

Mitochondrial Apoptosis ◽

Apoptosis Pathway ◽

Mitochondrial Apoptosis Pathway

Spermatogonial stem cells (SSCs) are the only adult stem cells that pass genes to the next generation and can be used in assisted reproductive technology and stem cell therapy. SSC cryopreservation is an important method for the preservation of immature male fertility. However, freezing increases the production of intracellular reactive oxygen species (ROS) and causes oxidative damage to SSCs. The aim of this study was to investigate the effect of melatonin on goat SSCs during cryopreservation and to explore its protective mechanism. We obtained SSCs from dairy goat testes by two-step enzymatic digestion and differential plating. The SSCs were cryopreserved with freezing media containing different melatonin concentrations. The results showed that 10-6 M of melatonin increased significantly the viability, total antioxidant capacity (T-AOC), and mitochondrial membrane potential of frozen-thawed SSCs, while it reduced significantly the ROS level and malondialdehyde (MDA) content ( P < 0.05 ). Further analysis was performed by western blotting, flow cytometry, and transmission electron microscopy (TEM). Melatonin improved significantly the enzyme activity and protein expression of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) ( P < 0.05 ), thereby activating the antioxidant defense system of SSCs. Furthermore, melatonin inhibited significantly the expression of proapoptotic protein (Bax) and increased the expression of antiapoptotic proteins (Bcl-2 and Bcl-XL) ( P < 0.05 ). The mitochondrial apoptosis pathway analysis showed that the addition of melatonin reduced significantly the mitochondrial swelling and vacuolation, and inhibited the release of cytochrome C from mitochondria into the cytoplasm, thereby preventing the activation of caspase-3 ( P < 0.05 ) and inhibiting SSC apoptosis. In addition, melatonin reduced significantly the autophagosome formation and regulated the expression of autophagy-related proteins (LC3-I, LC3-II, P62, Beclin1, and ATG7) ( P < 0.05 ), thereby reversing the freeze-induced excessive autophagy. In summary, melatonin protected goat SSCs during cryopreservation via antioxidant, antiapoptotic, and autophagic regulation.

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