Melatonin inhibits the apoptosis of rooster Leydig cells by suppressing oxidative stress via AKT-Nrf2 pathway activation

Dong, Yangyunyi; Zhao, Jing; Zhu, Qingyu; Liu, Hongyu; Wang, Jun; Lu, Wenfa

doi:10.1016/j.freeradbiomed.2020.06.024

Cited by 31 publications

(21 citation statements)

References 55 publications

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“…Melatonin is the strongest endogenous free radical scavenger, implicated in antioxidant systems and prevention of oxidative damage in cells. Melatonin can directly act on testes and alleviate testicular damage caused by oxidative stress, apoptosis, hyperthermia, and inflammation (Dong et al, 2020;Li et al, 2020b;Zhang et al, 2020a). In addition, melatonin has been reported to protect mitochondria by scavenging ROS, inhibiting the mitochondrial permeability transition pore (MPTP), activating uncoupling proteins (UCPs), and maintaining the optimal MMP, together maintaining mitochondrial homeostasis and preserving mitochondrial functions (Tan et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Melatonin Attenuates Chromium (VI)-Induced Spermatogonial Stem Cell/Progenitor Mitophagy by Restoration of METTL3-Mediated RNA N6-Methyladenosine Modification

Yang

et al. 2021

Front. Cell Dev. Biol.

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Spermatogonial stem cells (SSCs) are the basis of spermatogenesis, and any damage to SSCs may result in spermatogenic disorder and male infertility. Chromium (Cr) (VI) is a proven toxin, mutagen, and carcinogen, perpetually detrimental to environmental organisms due to its intricate and enduring detoxification process in vivo. Despite this, the deleterious effects of Cr (VI) on SSCs and the underlying mechanisms remain poorly understood. In this study, we identified that Cr (VI) impaired male reproductive system in mouse testes and induced mitochondrial dynamic imbalance and mitophagy in SSCs/progenitors. Cr (VI) also downregulated the RNA N6-methyladenosine (m6A) modification levels in mitochondrial dynamic balance and mitophagy genes in SSCs/progenitors. Inspiringly, the toxic effects of Cr (VI) could be relieved by melatonin pretreatment. Melatonin alleviated Cr (VI)-induced damage to male reproductive system and autophagy in mouse testes. Melatonin also attenuated Cr (VI)-induced cell viability loss and reactive oxygen species (ROS) generation, as well as mitochondrial dynamic disorders and mitophagy in SSCs/progenitors. The protective roles of melatonin against Cr (VI)-induced mitophagy were exerted by restoration of METTL3-mediated RNA m6A modification and activation of mitochondrial fusion proteins MFN2 and OPA1, as well as inhibition of the mitophagy BNIP3/NIX receptor pathway. Thus, our study provides novel insights into the molecular mechanisms for RNA m6A modification underlying the gene regulatory network responsible for mitochondrial dynamic balance, and also lays new experimental groundwork for treatment of Cr (VI)-induced damage to male fertility.

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Section: Discussionmentioning

confidence: 99%

Melatonin Attenuates Chromium (VI)-Induced Spermatogonial Stem Cell/Progenitor Mitophagy by Restoration of METTL3-Mediated RNA N6-Methyladenosine Modification

Yang

et al. 2021

Front. Cell Dev. Biol.

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“…The 8‐OHdG level in HEK293 cells induced by MGO (0.5, 1 and 2 mM) was detected according to the 8‐OHdG enzyme‐linked immunoassay kit instructions [82] …”

Section: Methodsmentioning

confidence: 99%

Potential Mechanisms of Methylglyoxal‐Induced Human Embryonic Kidney Cells Damage: Regulation of Oxidative Stress, DNA Damage, and Apoptosis

Liú

Cheng

Tang

et al. 2022

Chemistry & Biodiversity

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Methylglyoxal (MGO) is a reactive carbonyl species that can cause cellular damage and is closely related to kidney disease, especially diabetic nephropathy. The toxic effect of MGO (0.5, 1, and 2 mM) on human embryonic kidney (HEK293) cells and its underlying mechanisms were explored in this study. Cell viability, apoptosis and the signaling pathways were measured with MTT, fluorescent staining and western blot experiments, the results showed that MGO could induce oxidative stress and cell inflammation, the level of reactive oxygen species (ROS) increased, and p38MAPK, JNK and NF‐κB signaling pathways were activated. Meanwhile, MGO also induced DNA damage. The expression of DNA oxidative damage marker 8‐hydroxy‐2’‐deoxyguanosine (8‐OHdG) increased, the expression of double‐strand break marker γH2AX increased significantly, and ATM/Chk2/p53 DNA damage response signaling pathway was activated. Furthermore, the expression of the receptor for advanced glycation end products (RAGE) also increased. Finally, mitochondrial membrane potential (MMP) decreased, fluorescence intensity of Hoechst33258 increased, and the protein expression ratio of Bax/Bcl‐2 increased significantly after the treatment of MGO. These results demonstrated that MGO might induce HEK293 cells damage by regulating oxidative stress, inflammation, DNA damage, and cell apoptosis, which revealed the specific mechanisms of MGO‐induced damage to HEK293 cells.

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“…The HUVECs treated by acrolein were collected and lysed, and then centrifuge supernatant was used to detect 8-OHdG level. 38…”

Section: Detection Of 8-ohdg Levelmentioning

confidence: 99%

Mechanisms of acrolein induces toxicity in human umbilical vein endothelial cells: Oxidative stress, DNA damage response, and apoptosis

Liú

Cheng

Mei

et al. 2021

Environmental Toxicology

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Acrolein is a ubiquitous environmental pollutant that produced by the incomplete combustion of cigarette smoke, forest fires, petroleum fuels, plastic materials, and cooking fumes. Inhalation is a common form of people exposure to acrolein, increasing evidence demonstrates that acrolein impairs the cardiovascular system by targeting vascular endothelial cells. However, the molecular mechanism of the cytotoxicity of acrolein exposure on vascular endothelial cells remains unclear. This work focused on the toxicity of acrolein on human umbilical vein endothelial cells (HUVECs). The molecular mechanism was studied based on oxidative stress, DNA damage response (DDR), and mitochondrial apoptosis pathways. After HUVECs were treated with 12.5, 25, and 50 μM acrolein for 24 h, cell viability, cell colony formation, mitochondrial membrane potential, and adenosine triphosphate content significantly reduced, and acrolein increased intracellular reactive oxygen species, apoptosis rate, and 8-hydroxy-2 deoxyguanosine (8-OHdG) level. Furthermore, p38MAPK and c-Jun N-terminal kinase signaling pathways were activated in response to oxidative stress. Moreover, acrolein induced G0/G1phase arrest, promoted the expression of γ-H2AX, activated the DDR signaling pathway (Ataxia-Telangiectasia-Mutated [ATM] and Rad-3-related/Chk1 and ATM/Chk2), and triggered the consequent cell cycle checkpoints. Finally, the protein expression of Bax/Bcl-2 and cleaved Caspase-3 was up-regulated, suggesting apoptosis was induced by triggering the mitochondrial apoptosis pathway. All these results indicated that acrolein induced HUVECs cytotoxicity by regulating oxidative stress, DNA damage, and apoptosis. This study provides a novel perspective on the mechanism of acrolein-induced cardiovascular toxicity, it will be helpful for the prevention of acrolein-induced cardiovascular disease.

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Melatonin inhibits the apoptosis of rooster Leydig cells by suppressing oxidative stress via AKT-Nrf2 pathway activation

Cited by 31 publications

References 55 publications

Melatonin Attenuates Chromium (VI)-Induced Spermatogonial Stem Cell/Progenitor Mitophagy by Restoration of METTL3-Mediated RNA N6-Methyladenosine Modification

Melatonin Attenuates Chromium (VI)-Induced Spermatogonial Stem Cell/Progenitor Mitophagy by Restoration of METTL3-Mediated RNA N6-Methyladenosine Modification

Potential Mechanisms of Methylglyoxal‐Induced Human Embryonic Kidney Cells Damage: Regulation of Oxidative Stress, DNA Damage, and Apoptosis

Mechanisms of acrolein induces toxicity in human umbilical vein endothelial cells: Oxidative stress, DNA damage response, and apoptosis

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