Organic extracts in PM2.5 are the major triggers to induce ferroptosis in SH-SY5Y cells

Guo, Can-Can; Lyu, Yi; Xia, Shuangshuang; Ren, Xue‐Ke; Li, ZhaoFei; Tian, Fengjie; Zheng, Junhua

doi:10.1016/j.ecoenv.2022.114350

Cited by 11 publications

(7 citation statements)

References 39 publications

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“…In the present study, we found 17 metabolites, including amino acids (e.g., threonine, leucine, and lysine), that were associated with PM 2.5 and specific constituents. Many studies show that exposure to PM 2.5 is associated with reduced glutathione (GSH) levels, suggesting that PM 2.5 exposure may induce oxidative stress. , Oxidative stress can activate mTORC1 signaling through several mechanisms, such as promoting GSH synthesis and protein translation, eventually leading to the elevated expression of amino acids. − Our present study shows that threonine mediates a considerable proportion of the inverse association between specific PM 2.5 constituents and NBNA scores. In support of our findings, previous epidemiological studies demonstrated that PM 2.5 may disrupt plasma threonine and threonine metabolism pathways, which play a critical role in mTOR activity and certain stages of brain development. ,,, …”

Section: Discussionsupporting

confidence: 48%

Gestational Exposure to PM_2.5 and Specific Constituents, Meconium Metabolites, and Neonatal Neurobehavioral Development: A Cohort Study

Lu,

Liu,

Chen

et al. 2024

Environ. Sci. Technol.

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Exposure to fine particulate matter (PM2.5) during pregnancy has been inversely associated with neonatal neurological development. However, the associations of exposure to specific PM2.5 constituents with neonatal neurological development remain unclear. We investigated these associations and examined the mediating role of meconium metabolites in a Chinese birth cohort consisting of 294 mother–infant pairs. Our results revealed that exposure to PM2.5 and its specific constituents (i.e., organic matter, black carbon, sulfate, nitrate, and ammonium) in the second trimester, but not in the first or third trimester, was inversely associated with the total neonatal behavioral neurological assessment (NBNA) scores. The PM2.5 constituent mixture in the second trimester was also inversely associated with NBNA scores, and sulfate was identified as the largest contributor. Furthermore, meconium metabolome analysis identified four metabolites, namely, threonine, lysine, leucine, and saccharopine, that were associated with both PM2.5 constituents and NBNA scores. Threonine was identified as an important mediator, accounting for a considerable proportion (14.53–15.33%) of the observed inverse associations. Our findings suggest that maternal exposure to PM2.5 and specific constituents may adversely affect neonatal behavioral development, in which meconium metabolites may play a mediating role.

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Section: Discussionsupporting

confidence: 48%

Gestational Exposure to PM_2.5 and Specific Constituents, Meconium Metabolites, and Neonatal Neurobehavioral Development: A Cohort Study

Lu,

Liu,

Chen

et al. 2024

Environ. Sci. Technol.

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“…The method is adapted based on our previous publication (Guo et al, 2022). Briefly, the PM 2.5 was collected from December 2020 to February 2021 with the TH‐1000CII intelligent traffic air particles sampler (Wuhan Tianhong Environmental Protection Industry, China) near the traffic artery in Taiyuan, China.…”

Section: Methodsmentioning

confidence: 99%

“…Our previous study found that PM 2.5 can cause ferroptosis in SH‐SY5Y cells, but the specific mechanism is unclear (Guo et al, 2022). ERS is a pervasive stress‐defense mechanism in the eukaryotic cells (Qi & Chen, 2019).…”

Section: Introductionmentioning

confidence: 99%

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PM_2.5 induces autophagy‐dependent ferroptosis by endoplasmic reticulum stress in SH‐SY5Y cells

Guo

Lyu

et al. 2023

J of Applied Toxicology

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Fine particulate matter (PM2.5) has been a global environmental problem threatening public health in recent years. PM2.5 exposure was associated with an increased risk of neurodegenerative diseases related to neuronal apoptosis. Ferroptosis is a nonapoptotic form of programmed the cell death, characterized by excess iron‐dependent lipid peroxidation products. Whether PM2.5 could induce ferroptosis in cells and thus be involved in its neurotoxicity is unknown. In this study, we found that PM2.5 induced endoplasmic reticulum stress, apoptosis, autophagy, and ferroptosis in neuroblastoma human neuroblastoma cells (SH‐SY5Y). Interestingly, ferroptosis was the predominant form of mortality in the presence of high doses of PM2.5 exposure. In addition, the endoplasmic reticulum stress inhibitor 4‐phenylbutyric acid (4‐PBA) inhibited PM2.5‐induced cellular autophagy, apoptosis, and ferroptosis. Autophagy inhibitors chloroquine (CQ) alleviated PM2.5‐induced ferroptosis but did not reverse apoptosis. We also found that inhibition of both endoplasmic reticulum stress and autophagy reversed the PM2.5‐induced increase in the expression level of cytophagy nuclear receptor coactivator 4 (NCOA4). Our results suggested that PM2.5‐induced ferroptosis in SH‐SY5Y cells was autophagy‐dependent ferroptosis due to endoplasmic reticulum stress, which might be associated with the elevation of iron content caused by NCOA4‐mediated ferritin autophagy.

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“… 10 , 11 Guo et al, demonstrated that organic extracts in PM 2.5 induced ferroptosis of SH-SY5Y cells. 12 Autophagic-lysosomal dysfunction was also investigated in Neuro-2a cells exposed to PM 2.5 , leading to lysosome membrane permeabilization-associated cell death. 13 Nevertheless, the specific mechanism of neurotoxicity caused by PM 2.5 remains unclear.…”

Section: Introductionmentioning

confidence: 99%

PM _2.5 induced neurotoxicity through unbalancing vitamin B12 metabolism by gut microbiota disturbance

Zhu,

Xia,

Wang

et al. 2023

Gut Microbes

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Fine particulate matter (PM 2.5 ) in the atmosphere is easily accompanied by toxic and harmful substances, causing serious harm to human health, including cognitive impairment. Vitamin B12 (VitB12) is an essential micronutrient that is synthesized by bacteria and contributes to neurotransmitter synthesis as a nutrition and signaling molecule. However, the relationship between VitB12 attenuation of cognitive impairment and intestinal microbiota regulation in PM 2.5 exposure has not been elucidated. In this study, we demonstrated that PM 2.5 caused behavioral defects and neuronal damage in Caenorhabditis elegans ( C. elegans ), along with significant gene expression changes in neurotransmitter receptors and a decrease in VitB12 content, causing behavioral defects and neuronal damage in C. elegans . Methylcobalamin (MeCbl), a VitB12 analog, alleviated PM 2.5 -induced neurotoxicity in C. elegans . Moreover, using in vivo and in vitro models, we discovered that long-term exposure to PM 2.5 led to changes in the structure of the gut microbiota, resulting in an imbalance of the VitB12-associated metabolic pathway followed by cognitive impairment. MeCbl supplementation could increase the diversity of the bacteria, reduce harmful substance contents, and restore the concentration of short-chain fatty acids (SCFAs) and neurotransmitters to the level of the control group to some degree. Here, a new target to mitigate the harm caused by PM 2.5 was discovered, supplying MeCbl for relieving intestinal and intracellular neurotransmitter disorders. Our results also provide a reference for the use of VitB12 to target the adjustment of the human intestinal microbiota to improve metabolic disorders in people exposed to PM 2.5 .

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Organic extracts in PM2.5 are the major triggers to induce ferroptosis in SH-SY5Y cells

Cited by 11 publications

References 39 publications

Gestational Exposure to PM_2.5 and Specific Constituents, Meconium Metabolites, and Neonatal Neurobehavioral Development: A Cohort Study

Gestational Exposure to PM_2.5 and Specific Constituents, Meconium Metabolites, and Neonatal Neurobehavioral Development: A Cohort Study

PM_2.5 induces autophagy‐dependent ferroptosis by endoplasmic reticulum stress in SH‐SY5Y cells

PM _2.5 induced neurotoxicity through unbalancing vitamin B12 metabolism by gut microbiota disturbance

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Organic extracts in PM2.5 are the major triggers to induce ferroptosis in SH-SY5Y cells

Cited by 11 publications

References 39 publications

Gestational Exposure to PM2.5 and Specific Constituents, Meconium Metabolites, and Neonatal Neurobehavioral Development: A Cohort Study

Gestational Exposure to PM2.5 and Specific Constituents, Meconium Metabolites, and Neonatal Neurobehavioral Development: A Cohort Study

PM2.5 induces autophagy‐dependent ferroptosis by endoplasmic reticulum stress in SH‐SY5Y cells

PM 2.5 induced neurotoxicity through unbalancing vitamin B12 metabolism by gut microbiota disturbance

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Gestational Exposure to PM_2.5 and Specific Constituents, Meconium Metabolites, and Neonatal Neurobehavioral Development: A Cohort Study

Gestational Exposure to PM_2.5 and Specific Constituents, Meconium Metabolites, and Neonatal Neurobehavioral Development: A Cohort Study

PM_2.5 induces autophagy‐dependent ferroptosis by endoplasmic reticulum stress in SH‐SY5Y cells

PM _2.5 induced neurotoxicity through unbalancing vitamin B12 metabolism by gut microbiota disturbance