The activated ATM/AMPK/mTOR axis promotes autophagy in response to oxidative stress-mediated DNA damage co-induced by molybdenum and cadmium in duck testes

Pu, Wenjing; Chu, Xuesheng; Guo, Huiling; Huang, Gang; Cui, Ting; Huang, Bingyan; Dai, Xueyan; Zhang, Caiying

doi:10.1016/j.envpol.2022.120574

Cited by 13 publications

(15 citation statements)

References 53 publications

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“…Existing evidence supports that ischemic is a seriously harmful factor for fat grafting that especially results in the death of adipocytes 4,31 . Autophagy activation during ischemia facilitates the clearance of damaged organelles to maintain metabolic homeostasis, which mainly depends on AMPK‐mediated mTOR inhibition 20,21,26,27 . Here, we confirmed that the increase of mTOR pathway and the decrease of autophagy occurs with the peak of adipocyte death, providing evidence that these is an intrinsic link among mTOR, autophagy and adipocyte death at the early stage of fat grafting.…”

Section: Discussionsupporting

confidence: 76%

“…4,31 Autophagy activation during ischemia facilitates the clearance of damaged organelles to maintain metabolic homeostasis, which mainly depends on AMPK-mediated mTOR inhibition. 20,21,26,27 Here, we confirmed that the increase of mTOR pathway and the decrease of autophagy occurs with the peak of adipocyte death, providing evidence that these is an intrinsic link among mTOR, autophagy and adipocyte death at the early stage of fat grafting. Thus, rapamycin, a specific mTOR inhibitor, was employed as an autophagy activator for rescuing cell death during ischemia and assisting fat grafting.…”

Section: Discussionsupporting

confidence: 75%

“…19,[23][24][25] Regarding the mechanism, recent studies have shown that autophagy activation in the ischemic stage mainly depends on Adenosine 5′-monophosphate-activated protein kinase (AMPK)mediated inhibition of the mammalian target of rapamycin (mTOR). [26][27][28] It is generally believed that moderate autophagy is protective, while dysregulated autophagy has implications for health and disease. 14,15,23 However, the effect and mechanism of autophagy on fat graft survival have yet been reported.…”

Section: Introductionmentioning

confidence: 99%

“…Mitochondrial quality control mediated by mitophagy prevents the occurrence of irreversible cell damage 19,23–25 . Regarding the mechanism, recent studies have shown that autophagy activation in the ischemic stage mainly depends on Adenosine 5′‐monophosphate‐activated protein kinase (AMPK)‐mediated inhibition of the mammalian target of rapamycin (mTOR) 26–28 …”

Section: Introductionmentioning

confidence: 99%

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Activation of moderate autophagy promotes survival of fat graft

Pei,

Zhu,

Yang

et al. 2023

The FASEB Journal

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Clinically unpredictable retention following fat grafting remains outstanding problems because of the unrevealed mechanism of grafted fat survival. The role of autophagy, a process to maintain cellular homeostasis through recycling cellular debris, has yet been to be reported in fat grafting. This study aims to improve the survival of fat grafting through the autophagy. First, the relationship between cell death and autophagy in the early stage of fat grafting was evaluated through immunostaining, RNA sequencing, and western blot. Next, rapamycin, an autophagic agonist, was used for the culturing of adipose‐derived stem cells and adipocytes during ischemia. Cell death, autophagy, and reactive oxygen species (ROS) were assayed. Finally, rapamycin was used to assist fat grafting in nude mice. The results demonstrated that the peak of cell death at the early stage of fat grafting was accompanied by a decrease in autophagy. In vitro, during ischemia, 25 nM was confirmed as the optimal dose of rapamycin that reduces cell death with enhanced autophagy and mitophagy, improved mitochondrial quality as well as decreased ROS accumulation. In vivo, promoted mitophagy, alleviated oxidative stress, and decreased cell apoptosis of rapamycin‐treated fat grafts were observed in the early stage. In addition, rapamycin increased the survival of fat grafts with increased neovascularization and reduced fibrosis. We suggested that moderate autophagy induced by rapamycin contribute to enhanced ischemic tolerance and long term survival of fat grafts through mitochondrial quality control.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Activation of moderate autophagy promotes survival of fat graft

Pei,

Zhu,

Yang

et al. 2023

The FASEB Journal

View full text Add to dashboard Cite

show abstract

“…Autophagy is a crucial intracellular breakdown pathway that maintains the homeostatic balance in an organism [ 49 ]. However, it remains unclear whether autophagy is activated or inhibited during heavy metal poisoning [ 50 , 51 ]. In mouse kidneys and rat osteoblasts, Pb and Cd enhance the activation of autophagy [ 52 , 53 ].…”

Section: Discussionmentioning

confidence: 99%

Rat Hepatocytes Protect against Lead–Cadmium-Triggered Apoptosis Based on Autophagy Activation

Xue,

Liu,

Yin

et al. 2024

Toxics

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Lead and cadmium are foodborne contaminants that threaten human and animal health. It is well known that lead and cadmium produce hepatotoxicity; however, defense mechanisms against the co-toxic effects of lead and cadmium remain unknown. We investigated the mechanism of autophagy (defense mechanism) against the co-induced toxicity of lead and cadmium in rat hepatocytes (BRL-3A cells). Cultured rat liver BRL-3A cell lines were co-cultured with 10, 20, 40 μM lead and 2.5, 5, 10 μM cadmium alone and in co-culture for 12 h and exposed to 5 mM 3-Methyladenine (3-MA), 10 μM rapamycin (Rapa), and 50 nM Beclin1 siRNA to induce cellular autophagy. Our results show that treatment of BRL-3A cells with lead and cadmium significantly decreased the cell viability, increased intracellular reactive oxygen species levels, decreased mitochondrial membrane potential levels, and induced apoptosis, which are factors leading to liver injury, and cell damage was exacerbated by co-exposure to lead–cadmium. In addition, the results showed that lead and cadmium co-treatment induced autophagy. We further observed that the suppression of autophagy with 3-MA or Beclin1 siRNA promoted lead–cadmium-induced apoptosis, whereas enhancement of autophagy with Rapa suppressed lead–cadmium-induced apoptosis. These results demonstrated that co-treatment with lead and cadmium induces apoptosis in BRL-3A cells. Interestingly, the activation of autophagy provides cells with a self-protective mechanism against induced apoptosis. This study provides insights into the role of autophagy in lead–cadmium-induced apoptosis, which may be beneficial for the treatment of lead–cadmium-induced liver injury.

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Environmentally relevant levels of Cd and Mo coexposure induces ferroptosis and excess ferritinophagy through AMPK/mTOR axis in duck myocardium

Huang,

Nie,

Dai

et al. 2024

Environmental Toxicology

Self Cite

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Cadmium (Cd) and excess molybdenum (Mo) are multiorgan toxic, but the detrimental impacts of Cd and/or Mo on poultry have not been fully clarified. Thence, a 16‐week sub‐chronic toxic experiment was executed with ducks to assess the toxicity of Cd and/or Mo. Our data substantiated that Cd and Mo coexposure evidently reduced GSH‐Px, GSH, T‐SOD, and CAT activities and elevated H2O2 and MDA concentrations in myocardium. What is more, the study suggested that Cd and Mo united exposure synergistically elevated Fe2+ content in myocardium and activated AMPK/mTOR axis, then induced ferroptosis by obviously upregulating ACSL4, PTGS2, and TFRC expression levels and downregulating SLC7A11, GPX4, FPN1, FTL1, and FTH1 expression levels. Additionally, Cd and Mo coexposure further caused excessive ferritinophagy by observably increasing autophagosomes, the colocalization of endogenous FTH1 and LC3, ATG5, ATG7, LC3II/LC3I, NCOA4, and FTH1 expression levels. In brief, this study for the first time substantiated that Cd and Mo united exposure synergistically induced ferroptosis and excess ferritinophagy by AMPK/mTOR axis, finally augmenting myocardium injure in ducks, which will offer an additional view on united toxicity between two heavy metals on poultry.

show abstract

The activated ATM/AMPK/mTOR axis promotes autophagy in response to oxidative stress-mediated DNA damage co-induced by molybdenum and cadmium in duck testes

Cited by 13 publications

References 53 publications

Activation of moderate autophagy promotes survival of fat graft

Activation of moderate autophagy promotes survival of fat graft

Rat Hepatocytes Protect against Lead–Cadmium-Triggered Apoptosis Based on Autophagy Activation

Environmentally relevant levels of Cd and Mo coexposure induces ferroptosis and excess ferritinophagy through AMPK/mTOR axis in duck myocardium

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