ROS is the major player in regulating altered autophagy and lifespan insin-3mutants ofC. elegans

Sharma, Meenakshi; Pandey, Raju; Saluja, Daman

doi:10.1080/15548627.2018.1474312

Cited by 43 publications

(50 citation statements)

References 90 publications

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“…4 B). In many studies, mROS have been implicated in autophagy [18] , [19] , [20] . Consistent with these studied, 5-ALA-PDT increased LC3-II/β-actin protein level, which was significantly attenuated after treatment with Mito-TEMPO ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Efficacy of 5-aminolevulinic acid–based photodynamic therapy against keloid compromised by downregulation of SIRT1-SIRT3-SOD2-mROS dependent autophagy pathway

Liu

Ouyang

et al. 2019

Redox Biology

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Keloids exhibit cancer-like properties without spontaneous regression and usually recur post excision. Although photodynamic therapy (PDT) is a promising treatment, details of the mechanisms remain to be elucidated. In this study, we investigated mechanisms involved in 5-Aminolevulinic Acid (5-ALA)–based PDT against keloid. Found that 5-ALA-PDT induced superoxide anion-dependent autophagic cell death. Application of autophagy inhibitor 3-Methyladenine (3-MA) significantly prevented the effect that 5-ALA-PDT induced keloid–derived fibroblasts death, but Z-VAK-FMK (apoptotic inhibitor) did not. Interestingly, 5-ALA-PDT promoted the SIRT3 protein expression and the activity of mitochondrial superoxide dismutase 2 (SOD2), but SIRT1 protein expression level was decreased. SOD2 as a key enzyme can decrease mitochondrial ROS (mROS) level, Deacetylation of SOD2 by SIRT3 regulates SOD2 enzymatic activity has been identified. Then we explored SOD2 acetylation level with immunoprecipitation, found that 5-ALA-PDT significantly increased the acetylation levels of SOD2. In order to confirm deacetylation of SOD2 regulated by SIRT3, 3-TYP (SIRT3 inhibitor) was used. Found that inhibition of SIRT3 by 3-TYP significantly increased the level of SOD2 acetylation level compared with control group or 5-ALA-PDT group. To explore the connection of SIRT1 and SIRT3, cells were treated with EX527(SIRT1 inhibitor) or SRT1720 (SIRT1 activator), and EX527 increased SIRT3 protein level, however, SRT1720 displayed the opposite effect in the present or absence of 5-ALA-PDT. Moreover SIRT1-inhibited cells are more resistant to 5-ALA-PDT and showing decreased ROS accumulation. These results may demonstrate that 5-ALA-PDT induced SIRT1 protein level decreased, which promoted the effect of SIRT3 increased activity of SOD2 that can reduce mROS level, and then compromised 5-ALA-PDT induced autophagic cell death.

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Section: Resultsmentioning

confidence: 99%

Efficacy of 5-aminolevulinic acid–based photodynamic therapy against keloid compromised by downregulation of SIRT1-SIRT3-SOD2-mROS dependent autophagy pathway

Liu

Ouyang

et al. 2019

Redox Biology

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“…Given that ROS can also affect autophagy level, to further determine the effects of H 2 O 2 on MSC autophagy, we examined LC‐3B II/I ratio and p62 expression in the Rapa + H 2 O 2 co‐treatment (1.0, 10.0 and 100.0 μmol/L) groups. The results showed that LC‐3B II/I ratio increased and p62 expression decreased in the Rapa and Rapa + H 2 O 2 co‐treatment groups relative to those in the Control and D‐gal Control groups ( P < .01, Figure A,B).…”

Section: Resultsmentioning

confidence: 99%

Autophagy inhibits the mesenchymal stem cell aging induced by D‐galactose through ROS/JNK/p38 signalling

Zhang

Chen

et al. 2019

Clin Exp Pharma Physio

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Autophagy and cellular senescence are two critical responses of mammalian cells to stress and may have a direct relationship given that they respond to the same set of stimuli, including oxidative stress, DNA damage, and telomere shortening. Mesenchymal stem cells (MSCs) have emerged as reliable cell sources for stem cell transplantation and are currently being tested in numerous clinical trials. However, the effects of autophagy on MSC senescence and corresponding mechanisms have not been fully evaluated. Several studies demonstrated that autophagy level increases in aging MSCs and the downregulation of autophagy can delay MSC senescence, which is inconsistent with most studies that showed autophagy could play a protective role in stem cell senescence. To further study the relationship between autophagy and MSC senescence and explore the effects and mechanisms of premodulated autophagy on MSC senescence, we induced the up-or down-regulation of autophagy by using rapamycin (Rapa) or 3-methyladenine, respectively, before MSC senescence induced by D-galactose (D-gal). Results showed that pretreatment with Rapa for 24 hours remarkably alleviated MSC aging induced by D-gal and inhibited ROS generation. p-Jun N-terminal kinases (JNK) and p-38 expression were also clearly decreased in the Rapa group. Moreover, the protective effect of Rapa on MSC senescence can be abolished by enhancing the level of ROS, and p38 inhibitor can reverse the promoting effect of H 2 O 2 on MSC senescence. In summary, the present study indicates that autophagy plays a protective role in MSC senescence induced by D-gal, and ROS/JNK/p38 signalling plays an important mediating role in autophagydelaying MSC senescence. K E Y W O R D S autophagy, mesenchymal stem cells, ROS/JNK/p38 signalling, senescence S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Zhang D, Chen Y, Xu X, et al. Autophagy inhibits the mesenchymal stem cell aging induced by D-galactose through ROS/JNK/p38 signalling. Clin Exp Pharmacol Physiol. 2020;47:466-477. https ://doi.

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“…To further explore the mechanism of toxicity of SiO 2 NPs, we examined the expression levels of oxidative stress-related genes. The five nematode sod genes (sod-1, sod-2, sod-3, sod-4, sod-5) are homologs of mammalian cytoplasmic, mitochondrial, and extracellular superoxide dismutase (SOD1, SOD2, SOD3), and the three nematode ctl genes (ctl-1, ctl-2, ctl-3) are homologs of mammalian cytoplasmic and peroxisomal catalase (CAT) (Sharma et al, 2018). The sod genes are involved in superoxide dismutase and protein homodimerization activity, and the ctl genes are related to catalase activity (Zelko et al, 2002;Song et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Silica nanoparticles enhance germ cell apoptosis by inducing reactive oxygen species (ROS) formation in Caenorhabditis elegans

et al. 2020

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Silica nanoparticles (SiO 2 NPs) are widely used in daily life and can enter organisms through several pathways, often causing unpredictable toxicity. Although SiO 2 NPs are known to cause damage to the respiratory system, little is known about their oral toxicity, and their potential harm to the reproductive system is unclear. In this study, we used a Caenorhabditis elegans model to clarify SiO 2 NPs oral toxicity in vivo and explore their effect on the reproductive system. We exposed C. elegans to 0.25, 0.5 and 1 mg /mL SiO 2 NPs for 24 hr. Our results showed that SiO 2 NPs exposure for 24 hr did not affect nematode survival rates, but did affect, to varying degrees, the reproduction, development, and movement of nematodes, with nematode fecundity being the most sensitive to SiO 2 NPs toxicity. The NPs exposed group showed enhanced germ cell apoptosis and increased oxidative stress as seen through an increase in ROS and malondialdehyde (MDA), and decrease in reduced glutathione (GSH). N-acetyl-L-cysteine (NAC), an antioxidant, negated SiO 2 NPs effect on germ cells and restored nematodes reproductive ability. We also found that SiO 2 NPs could affect the expression of genes related to metal detoxification, oxidative stress, and apoptosis. The expression of metallothionein coding genes mtl-1 and mtl-2 changed most significantly among the tested genes. We demonstrated that SiO 2 NPs could enhance germ cell apoptosis by inducing oxidative stress, providing a new area for studies of the mechanism of SiO 2 NP toxicity.

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ROS is the major player in regulating altered autophagy and lifespan insin-3mutants ofC. elegans

Cited by 43 publications

References 90 publications

Efficacy of 5-aminolevulinic acid–based photodynamic therapy against keloid compromised by downregulation of SIRT1-SIRT3-SOD2-mROS dependent autophagy pathway

Efficacy of 5-aminolevulinic acid–based photodynamic therapy against keloid compromised by downregulation of SIRT1-SIRT3-SOD2-mROS dependent autophagy pathway

Autophagy inhibits the mesenchymal stem cell aging induced by D‐galactose through ROS/JNK/p38 signalling

Silica nanoparticles enhance germ cell apoptosis by inducing reactive oxygen species (ROS) formation in <i>Caenorhabditis elegans</i>

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