Activation of mitochondria-mediated apoptotic pathway in tri-ortho-cresyl phosphate-induced delayed neuropathy

Zou, Chaoshuang; Kou, Ruirui; Gao, Yuan; Xie, Keqin; Song, Fuyong

doi:10.1016/j.neuint.2013.03.013

Cited by 24 publications

(9 citation statements)

References 38 publications

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“…Jiang et al [2] reported that the down-regulated expression of glutamine synthetase (GS) might be associated with the delayed neuropathy induced by TOCP through the disruption of homeostasis of the glutamate (Glu)-glutamine (Gln) cycle and cytosolic calcium concentration. Zou et al [32] found that the delayed neuropathy induced by TOCP might be mediated by the activation of mitochondrial apoptotic pathway. It was reported that the disruption of neurofilament (NF) homeostasis in peripheral nerves might be an early molecular event in the development of the delayed neuropathy induced by TOCP [36,37].…”

Section: Discussionmentioning

confidence: 99%

“…Hens in delayed neuropathy model group were administered by gavage with a single dose of 750 mg/kg TOCP. This dosage of TOCP was commonly used to develop an experimental animal model of delayed neuropathy in hens [20,32]. Firstly, the hens in Apelin-13 treatment group were administered by gavage with a single dose of 750 mg/kg TOCP, and then the hens were treated with intraperitoneal injection with 10 nmol/kg Apelin-13 one time per day for 21 days.…”

Section: Animal Treatment and Groupmentioning

confidence: 99%

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RETRACTED ARTICLE: Apelin-13 Prevents the Delayed Neuropathy Induced by Tri-ortho-cresyl Phosphate Through Regulation the Autophagy Flux in Hens

et al. 2015

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Organophosphate-induced delayed neuropathy (OPIDN) is pathologically characterized by the swollen axon containing aggregations of microtubules, neurofilaments, smooth endoplasmic reticulum and multivesicular vesicles. At present, the exact mechanism of OPIDN is unclear and the effective therapeutic methods is not available to counter this syndrome. Recent studies had shown that the autophagy was involved in OPIDN. The adipocytokine Apelin is a peptide, Apelin and its receptor are abundantly expressed in the nervous system. Recent researches illuminated that Apelin was neuroprotective factor and Apelin could regulate the autophagy in vivo and vitro model. So we investigated the effect of Apelin-13 on the OPIDN induced by Tri-ortho-cresyl phosphate (TOCP) in hens and explored the role of autophagy in Apelin-13 preventing OPIDN. Adult Roman hens were given a single dose of 750 mg/kg TOCP by gavage for 21 days to induce OPIDN, and neural dysfunction were detected, and the formation of autophagosomes in spinal cord neurons was observed by transmission electron microscopy, and the molecular markers of autophagy microtubule-associated protein light chain-3 (LC3) and the autophagy substrates p62/SQSTM1 were determined by Western blot analysis. The results demonstrated that the obvious neurological dysfunction such as hindlimb paralysis and paralysis of gait was present, the number of autophagosomes in the neurons of spinal cords was significantly increased, the level of LC3-II and p62 expressions and the ratio of LC3-II/LC3-I in spinal cords and sciatic nerve were significantly increased in the OPIDN model group compared with the control group. Compared with the OPIDN model group, the neurological dysfunction of tens was obviously reduced, the clinical signs scores was significantly decreased, the number of autophagosomes in the neurons of hen spinal cords was significantly decreased, the level of LC3-II and p62 expressions and the ratio of LC3-II/LC3-I in spinal cords and sciatic nerve were significantly decreased in Apelin-13 treatment group. Our results suggested that Apelin-13 prevented against the OPIDN induced by TOCP in hens, which the mechanism might be associated with regulation autophagy flux by Apelin-13.

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Section: Discussionmentioning

confidence: 99%

Section: Animal Treatment and Groupmentioning

confidence: 99%

RETRACTED ARTICLE: Apelin-13 Prevents the Delayed Neuropathy Induced by Tri-ortho-cresyl Phosphate Through Regulation the Autophagy Flux in Hens

et al. 2015

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“…A variety of environmental chemicals, including the pesticides rotenone and chlorpyrifos, and the flame retardant tri- ortho -chresyl phosphate were previously identified as inhibitors of the mitochondrial electron transport chain, a pathway that can result in increased formation of reactive oxygen species and ultimately the induction of apoptosis (Jang et al . 2015; Zou et al . 2013).…”

Section: Discussionmentioning

confidence: 99%

In vitro cardiotoxicity assessment of environmental chemicals using an organotypic human induced pluripotent stem cell-derived model

Sirenko¹,

Grimm

Ryan

et al. 2017

Toxicology and Applied Pharmacology

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An important target area for addressing data gaps through in vitro screening is the detection of potential cardiotoxicants. Despite the fact that current conservative estimates relate at least 23% of all cardiovascular disease cases to environmental exposures, the identities of the causative agents remain largely uncharacterized. Here, we evaluate the feasibility of a combinatorial in vitro/in silico screening approach for functional and mechanistic cardiotoxicity profiling of environmental hazards using a library of 69 representative environmental chemicals and drugs. Human induced pluripotent stem cell-derived cardiomyocytes were exposed in concentration-response for 30 min or 24 hrs and effects on cardiomyocyte beating and cellular and mitochondrial toxicity were assessed by kinetic measurements of intracellular Ca2+ flux and high-content imaging using the nuclear dye Hoechst 33342, the cell viability marker Calcein AM, and the mitochondrial depolarization probe JC-10. More than half of tested chemicals exhibited effects on cardiomyocyte rhythm after 30 min of exposure. After 24 hours, the effects on cell rhythm without cytotoxicity were observed in about one third of the compounds. Concentration-response data for in vitro bioactivity phenotypes were visualized using Toxicological Prioritization Index (ToxPi) and showed chemical class-specific clustering of environmental chemicals, including pesticides, flame retardants, and polycyclic aromatic hydrocarbons. For environmental chemicals with human exposure predictions, the activity-to-exposure ratios between modeled blood concentrations and in vitro bioactivity were between one and five orders of magnitude. These findings not only demonstrate that some ubiquitous environmental pollutants might have the potential to alter cardiomyocyte function at high exposures, but also indicate similarities in the mechanism of these effects both within and among chemicals and classes.

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“…Caspase activation is an indispensable event in the initiation of mitochondria-mediated apoptosis37 ) . Among the identified caspases, caspase 3 is thought to be the key enzyme that induces apoptosis.…”

Section: Discussionmentioning

confidence: 99%

2,5-hexanedione induced apoptosis in mesenchymal stem cells from rat bone marrow via mitochondria-dependent caspase-3 pathway

et al. 2015

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2,5-hexanedione (HD) induces apoptosis of nerve cells. However,the mechanism of HD-induced apoptosis remains unknown. Mesenchymal stem cells (MSCs) are multipotential stem cells with the ability to differentiate into various cell types. This study is designed to investigate the apoptosis induced by HD in rat bone marrow MSCs (BMSCs) and the related underlying mechanisms. The fifth generation of MSCs was treated with 0, 10, 20 and 40 mM HD respectively. The viability of BMSCs was observed by MTT. Apoptosis were estimated by Hoechst 33342 staining and TUNEL assay. The disruption of mitochondrial transmembrane potential (MMP) was examined by JC-1 staining. Moreover, the expression of Bax and Bcl-2, cytochrome c release, and caspase-3 activity were determined by real-time RT-PCR, Western blot and Spectrophotometry. Our results showed that HD induced apoptosis in MSCs in a dose dependent manner. Moreover, HD downregulated the Bcl-2 expression,upregulated the Bax expression and the Bax/Bcl-2 ratio, promoted the disruption of MMP, induced the release of cytochrome c from mitochondria to cytosol, and increased the activity of caspase-3 in MSCs. These results indicate that HD induces apoptosis in MSCs and the activated mitochondria-dependent caspase-3 pathway may be involved in the HD-induced apoptosis.

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Activation of mitochondria-mediated apoptotic pathway in tri-ortho-cresyl phosphate-induced delayed neuropathy

Cited by 24 publications

References 38 publications

RETRACTED ARTICLE: Apelin-13 Prevents the Delayed Neuropathy Induced by Tri-ortho-cresyl Phosphate Through Regulation the Autophagy Flux in Hens

RETRACTED ARTICLE: Apelin-13 Prevents the Delayed Neuropathy Induced by Tri-ortho-cresyl Phosphate Through Regulation the Autophagy Flux in Hens

In vitro cardiotoxicity assessment of environmental chemicals using an organotypic human induced pluripotent stem cell-derived model

2,5-hexanedione induced apoptosis in mesenchymal stem cells from rat bone marrow via mitochondria-dependent caspase-3 pathway

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