Fluorochloridone induces primary cultured Sertoli cells apoptosis: Involvement of ROS and intracellular calcium ions-mediated ERK1/2 activation

Liu, Luqing; Chang, Xiuli; Zhang, Yubin; Wu, Chunhua; Li, Rui; Tang, Liming; Zhou, Zhijun

doi:10.1016/j.tiv.2017.12.006

Cited by 25 publications

(12 citation statements)

References 34 publications

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“…We performed an apoptosis study in our system by pre-treating the cell lines with NAC to decrease the oxidative stress, and at the same time they were incubated with different treatments involving the Ca 2+ pathway. STS was used to induce a cytotoxicity response by inhibiting the PI3K/AKT signaling pathway [ 29 ] and Tg was used to decrease respiration selectively, with complex I substrates producing an increase in ER stress, resulting in an intracellular calcium overload that favors the activation of calcium-dependent calpains, according to Mohsin et al [ 30 ]. H 2 O 2 was used to directly activate IP3 receptors [ 31 ], and reagents such as DMSO were used to induce ER stress, increasing Ca 2+ levels through oxidative stress [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

High-Throughput Screen Detects Calcium Signaling Dysfunction in Hutchinson-Gilford Progeria Syndrome

Fafián-Labora

Morente-López

Toro

et al. 2021

IJMS

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Hutchinson–Gilford progeria syndrome (HGPS) is a deadly childhood disorder, which is considered a very rare disease. It is caused by an autosomal dominant mutation on the LMNA gene, and it is characterized by accelerated aging. Human cell lines from HGPS patients and healthy parental controls were studied in parallel using next-generation sequencing (NGS) to unravel new non-previously altered molecular pathways. Nine hundred and eleven transcripts were differentially expressed when comparing healthy versus HGPS cell lines from a total of 21,872 transcripts; ITPR1, ITPR3, CACNA2D1, and CAMK2N1 stood out among them due to their links with calcium signaling, and these were validated by Western blot analysis. It was observed that the basal concentration of intracellular Ca2+ was statistically higher in HGPS cell lines compared to healthy ones. The relationship between genes involved in Ca2+ signaling and mitochondria-associated membranes (MAM) was demonstrated through cytosolic calcium handling by means of an automated fluorescent plate reading system (FlexStation 3, Molecular Devices), and apoptosis and mitochondrial ROS production were examined by means of flow cytometry analysis. Altogether, our data suggest that the Ca2+ signaling pathway is altered in HGPS at least in part due to the overproduction of reactive oxygen species (ROS). Our results unravel a new therapeutic window for the treatment of this rare disease and open new strategies to study pathologies involving both accelerated and healthy aging.

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Section: Discussionmentioning

confidence: 99%

High-Throughput Screen Detects Calcium Signaling Dysfunction in Hutchinson-Gilford Progeria Syndrome

Fafián-Labora

Morente-López

Toro

et al. 2021

IJMS

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“…Second, the decrease in sperm quality may be related to the effects of FLC on sertoli cells. Liu et al [16] found that FLC could lead to apoptosis and induce the elevation of ROS levels, intracellular calcium levels, and ERK1/2 activation in sertoli cells. FLC could also perturb blood-testis-barrier (BTB)/sertoli cell barrier function through Arp3-mediated F-actin disorganization [17].…”

Section: Discussionmentioning

confidence: 99%

“…FLC toxicity studies indicated that the target organs were testes and epididymides of male animals, while FLC was almost non-toxic to female animals at the same dose [14, 15]. FLC could induce primary cultured sertoli cell apoptosis [16] and perturb blood-testis barrier/sertoli cell barrier function [17]. We found that the oral no-observable-adverse-effect level (NOAEL) in the 90-day subchronic toxicity test was 3 mg/kg/day in rats in our previous study [14, 18], which was an order of magnitude lower than reported by European Food Safety Authority (EFSA).…”

Section: Introductionmentioning

confidence: 99%

Low dose of flurochloridone affected reproductive system of male rats but not fertility and early embryonic development

Zhou

Zhu

et al. 2019

Reprod Biol Endocrinol

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Background Fluorochloridone (FLC) is a widely used herbicide, and its target organs are testes and epididymides. The Globally Harmonized System of Classification and Labelling of Chemicals classified FLC as Level 2-possibly cause fertility or fetal damage (no relevant data support). The maximum residue levels of FLC in processed crops have been reviewed in the latest European Food Safety Authority (EFSA) report in 2018. However, the toxic effect of FLC on fertility and early embryonic development is limited, and the health risk assessment of FLC needs further consideration. This study investigated the potential effects of FLC on fertility and early embryonic development in rats. Methods One hundred rats of each sex were divided into four groups including three FLC-treated groups at doses of 2 mg/kg, 5 mg/kg and 15 mg/kg, and a vehicle control group (0.5% (w/v) sodium carboxymethyl cellulose). Male and female rats were dosed for 9 and 2 consecutive weeks, intragastrically, prior to cohabitation and lasted throughout the mating period for males and continued until Gestation Day 7 (GD7) for females. Parameters such as weights and coefficients of reproductive organs, epididymal sperm number and motility, indexes of copulation, fecundity and fertility indexes, mating period, estrous cycle, corporalutea number, implantations, live, dead and resorbed fetuses, preimplantation loss rate, and postimplantation loss rate were observed in this study. Results Obvious toxicity of male reproductive system was found at the dose of 15 mg/kg including decreases in testicular and epididymal weight, also in sperm motility rate. Whereas the increase in sperm abnormality rate was observed. However, no significant effects of FLC were found on lutea count, implantations count, fetuses count and weight, live fetuses count (rate), dead fetuses count (rate), resorbed fetuses count (rate), placentas weight, fetuses gender, preimplantation loss (rate) and postimplantation loss (rate). Furthermore, FLC had no adverse effects on fertility and early embryonic development in rats. Conclusion The no-observable-adverse-effect level (NOAEL) of FLC on fertility and early embryonic development in rats was considered to be 5 mg/kg/day.

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“…Reactive oxygen species generation has also been involved in the initiation of β-Benzene Hexachloride induced apoptosis by activation of the JNKs (Shi et al, 2011). Nonylphenol and Fluorochloridone also induce apoptosis in Sertoli cells via induction of oxidative stress and ERK activation (Choi et al, 2014;Liu et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Cytotoxicity of mancozeb on Sertoli–germ cell co-culture system: Role of MAPK signaling pathway

et al. 2021

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Mancozeb (MZB) is a worldwide fungicide for the management of fungal diseases in agriculture and industrial contexts. Human exposure occurs by consuming contaminated plants, drinking water, and occupational exposure. There are reports on MZB’s reprotoxicity such as testicular structure damage, sperm abnormalities, and decrease in sperm parameters (number, viability, and motility), but its molecular mechanism on apoptosis in testis remains limited. To investigate the molecular mechanisms involved in male reprotoxicity induced by MZB, we used primary cultures of mouse Sertoli–germ cells. Cells were exposed to MZB (1.5, 2.5, and 3.5 μM) for 3 h to evaluate viability by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, reactive oxygen species (ROS) generation, and oxidative stress parameters (lipid peroxidation). Cell death and mitogen-activated protein kinase (MAPK) signaling were measured in these cells using flow cytometry and western blotting. In addition, some groups were exposed to N-acetylcysteine (NAC, 5 mM) in the form of co-treatment with MZB. Mancozeb reduced viability and increased the level of intracellular ROS, p38 and c-Jun N-terminal kinases (JNK) MAPK proteins phosphorylation, and apoptotic cell death, which could be blocked by NAC as an inhibitor of oxidative stress. The present study indicated for the first time the toxic manifestations of MZB on the Sertoli–germ cell co-culture. Redox imbalance and p38 and JNK signaling pathway activation might play critical roles in MZB-induced apoptosis in the male reproductive system.

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Fluorochloridone induces primary cultured Sertoli cells apoptosis: Involvement of ROS and intracellular calcium ions-mediated ERK1/2 activation

Cited by 25 publications

References 34 publications

High-Throughput Screen Detects Calcium Signaling Dysfunction in Hutchinson-Gilford Progeria Syndrome

High-Throughput Screen Detects Calcium Signaling Dysfunction in Hutchinson-Gilford Progeria Syndrome

Low dose of flurochloridone affected reproductive system of male rats but not fertility and early embryonic development

Cytotoxicity of mancozeb on Sertoli–germ cell co-culture system: Role of MAPK signaling pathway

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