Zearalenone (ZEA) is an estrogen‐like toxin produced by Fusarium that is widely found in cereals worldwide. In recent years, ZEA has been found to cause reproductive dysfunction in male animals, but ...the underlying mechanism remains unclear. This study examined the apoptosis of rat Sertoli cells induced by different concentrations (0, 5, 10, and 20 μmol/L) of ZEA via Fas‐Fas ligand and mitochondrial signaling pathway in vitro. Apoptosis rate was detected by flow cytometry. The mitochondrial membrane potential was detected by immunofluorescence assay and flow cytometry. Western Blot and qRT‐PCR were used to identify the signaling pathway. The results revealed that ZEA induced apoptosis of rat Sertoli cells, significantly reduced the transcription and expression of the anti‐apoptotic protein Bcl‐2, increased the transcription and expression of pro‐apoptotic proteins Bax and tBID, and Fas, FasL, FADD, and caspase‐8. ZEA also increased the activation of caspase‐8 and caspase‐9, and promoted the release of cytochrome C from mitochondria to cytoplasm. Moreover, addition of caspase‐8 inhibitor Z‐IETD‐FMK led to significant decrease in the mitochondrial membrane potential and apoptosis rate of the ZEA + Z‐IETD‐FMK group as compared to the ZEA treatment group. The release of cytochrome C from mitochondria to cytoplasm and the activation of caspase‐9 and caspase‐3 were significantly decreased in the ZEA + Z‐IETD‐FMK group. These results suggested that ZEA can induce apoptosis of rat Sertoli cells, activate the Fas‐Fas ligand signaling pathway and participate in the regulation of mitochondrial apoptosis pathway.
Cadmium is a persistent environmental pollutant whose neurotoxicity is of serious concern. Mitochondrial dysfunction and its mediated mitophagy and apoptosis are considered key events in Cd-induced ...neurological pathologies, but the exact molecular mechanism has not been fully elucidated. The aim of this study was to investigate the relationship between Cd-induced mitophagy and apoptosis and their role in Cd-induced neuronal death. Using the mitophagy inhibitor cyclosporine A (CsA), we found that the extent of mitophagy mediated by the PTEN-induced putative kinase protein 1 (PINK1)/E3 ubiquitin ligase (Parkin) pathway decreased, whereas the level of apoptosis and cell death increased in rat cerebral cortical neurons in vitro. Consistent with this, the knockdown of PINK1 also exacerbated Cd-induced apoptosis and neuronal death. Furthermore, the results of the in vivo experiments showed that Cd simultaneously activated both mitophagy and apoptosis and that the suppression of mitophagy by CsA aggravated Cd-induced apoptosis. In summary, our results indicate that PINK1/Parkin-mediated mitophagy exerts an important neuroprotective effect by inhibiting Cd-mediated apoptosis in rat cerebral cortical neurons both in vitro and in vivo. This work may allow the development of new therapeutic strategies for Cd-induced central nervous system disorders.
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•Cadmium-activated mitophagy mediates neuronal apoptosis via mitochondrial pathway.•Mitophagy inhibitor cyclosporine A aggravates cadmium-induced neuronal apoptosis.•PINK1 knockdown aggravates cadmium-induced apoptosis and neuronal death.
The complex microbial community in food environment is a major problem of human or animal health and safety. Mycotoxins and food-borne bacteria can both induce inflammation in the body and cause a ...series of changes in biological functions. In this study, mice were gavaged with low doses of ZEA, DON, or ZEA + DON, and then infected with L. monocytogenes. A cytokine microarray, including 40 inflammation-related serum cytokines, and proteomics were used to verify the effects of ZEA, DON, and ZEA + DON on the host inflammation and biological function after L. monocytogenes infection. The results showed that mononucleosis after bacterial infection was inhibited by ZEA, DON, and ZEA + DON, while the balance of macrophage differentiation was shifted toward M2-type. ZEA, DON, and ZEA + DON decreased the levels of serum proinflammatory cytokines IL-1β and IL-12 after infection. In addition, the signal of the NF-κB pathway was inhibited. Proteomic results showed that ZEA, DON, and ZEA + DON led to biological dysfunction in ribosomal and metabolic cells, primarily leading to abnormal ribosomal hyperfunction. This study showed that ZEA, DON, and ZEA + DON can aggravate disease progression by inhibiting the inflammatory response following foodborne bacterial infection. These metabolites may also disrupt normal biological functions, which may lead to ribosomal hyperfunction, making bacterial clearance more difficult.
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•ZEA, DON shifted the balance of macrophage to M2 type after bacterial infection.•The inflammatory cytokine network after infection was affected.•ZEA, DON had great influence on cell metabolism and ribosome function after infection.•The function of the ribosome was hyperactive.
Abstract
Hot extremes, ultraviolet (UV) radiation, and surface ozone all have prominent effects on human health and ecosystems. Here we show evidence that both hot extremes and high surface UV ...radiation at noon time occur concurrently in summer over the Yangtze Plain. Composite analysis suggests that hot extremes in summer are primarily caused by the westward extension of the Western Pacific Subtropical High, which leads to less clouds and consequently more downward solar radiation on the surface over the Yangtze Plain. It is found that surface UV radiation may be dominated by cloud variations, instead of stratospheric ozone during the hot extremes. Further analysis indicates that the hot extremes and high UV radiation, which play important roles in photochemistry in the troposphere, may result in more surface ozone. The concurrent hot extremes, strong UV radiation, and severe ozone pollutions over the Yangtze Plain in summer are likely to have dramatical influences on human health, which should be paid more attention.
Zearalenone (ZEA), a common mycotoxin in grains and animal feeds, has been associated with male reproductive disorders. However, the potential toxicity mechanism of ZEA is not fully understood. In ...this study, in vivo and in vitro models were used to explore the effects of ZEA on the blood–testis barrier (BTB) and related molecular mechanisms. First, male BALB/C mice were administered ZEA orally (40 mg/kg·bw) for 5–7 d. Sperm motility, testicular morphology, and expressions of BTB junction proteins and autophagy-related proteins were evaluated. In addition, TM4 cells (mouse Sertoli cells line) were used to delineate the molecular mechanisms that mediate the effects of ZEA on BTB. Our results demonstrated that ZEA exposure induced severe testicular damage in histomorphology and an ultrastructural, time-dependent decrease in the expression of blood–testis barrier junction-related proteins, accompanied by an increase in the expression of autophagy-related proteins. Additionally, similar to the in vitro results, the dose-dependent treatment of ZEA increased the level of cytoplasmic Ca2+ and the levels of the autophagy markers LC3-II and p62, in conjunction with a decrease in the BTB junction proteins occludin, claudin-11, and Cx43, with the dislocation of the gap junction protein Cx43. Meanwhile, inhibition of autophagy by CQ and 3-MA or inhibition of cytoplasmic Ca2+ by BAPTA-AM was sufficient to reduce the effects of ZEA on the TM4 cell BTB. To summarize, this study emphasizes the role of Ca2+-mediated autophagy in ZEA-induced BTB destruction, which deepens our understanding of the molecular mechanism of ZEA-induced male reproductive disorders.
Zearalenone (ZEA), one of the mycotoxins, exerts different mechanisms of toxicity in different cell types at different doses. It can not only stimulate cell proliferation but also inhibit cell ...viability, induce cell apoptosis, and cause cell death. Thus, the objective of this review is to summarize the available mechanisms and current evidence of what is known about the cell proliferation or cell death induced by ZEA. An increasing number of studies have suggested that ZEA promoted cell proliferation attributing to its estrogen-like effects and carcinogenic properties. What's more, many studies have indicated that ZEA caused cell death via affecting the distribution of the cell cycle, stimulating oxidative stress and inducing apoptosis. In addition, several studies have revealed that autophagy and some antioxidants can reverse the damage or cell death induced by ZEA. This review thoroughly summarized the metabolic process of ZEA and the molecular mechanisms of ZEA stimulating cell proliferation and cell death. It concluded that a low dose of ZEA can exert estrogen-like effects and carcinogenic properties, which can stimulate the proliferation of cells. While, in addition, a high dose of ZEA can cause cell death through inducing cell cycle arrest, oxidative stress, DNA damage, mitochondrial damage, and apoptosis.
Autophagic dysfunction is one of the main mechanisms of cadmium (Cd)-induced neurotoxicity. Puerarin (Pue) is a natural antioxidant extracted from the medicinal and edible homologous plant
. Studies ...have shown that Pue has neuroprotective effects in a variety of brain injuries, including Cd-induced neuronal injury. However, the role of Pue in the regulation of autophagy to alleviate Cd-induced injury in rat cerebral cortical neurons remains unclear. This study aimed to elucidate the protective mechanism of Pue in alleviating Cd-induced injury in rat cerebral cortical neurons by targeting autophagy. Our results showed that Pue alleviated Cd-induced injury in rat cerebral cortical neurons in vitro and in vivo. Pue activates autophagy and alleviates Cd-induced autophagic blockade in rat cerebral cortical neurons. Further studies have shown that Pue alleviates the Cd-induced inhibition of autophagosome-lysosome fusion, as well as the inhibition of lysosomal degradation. The specific mechanism is related to Pue alleviating the inhibition of Cd on the expression levels of the key proteins Rab7, VPS41, and SNAP29, which regulate autophagosome-lysosome fusion, as well as the lysosome-related proteins LAMP2, CTSB, and CTSD. In summary, these results indicate that Pue alleviates Cd-induced autophagic dysfunction in rat cerebral cortical neurons by alleviating autophagosome-lysosome fusion dysfunction and lysosomal degradation dysfunction, thereby alleviating Cd-induced neuronal injury.
We designed this study to investigate whether cadmium induces caspase-independent apoptosis and to investigate the relationship between the caspase-dependent and caspase-independent apoptotic ...pathways. Cadmium (1.25-2.5 μM) induced oxidative stress in rat proximal tubular (rPT) cells, as seen in the reactive oxygen species levels; N-acetylcysteine prevented this. Cyclosporin A (CsA) prevented mitochondrial permeability transition pore opening and apoptosis; there was mitochondrial ultrastructural disruption, mitochondrial cytochrome c (cyt c) translocation to the cytoplasm, and subsequent caspase-9 and caspase-3 activation. Z-VAD-FMK prevented caspase-3 activation and apoptosis and decreased BNIP-3 (Bcl-2/adenovirus E1B 19-kDa interacting protein 3) expression levels and apoptosis-inducing factor/endonuclease G (AIF/Endo G) translocation. Simultaneously, cadmium induced prominent BNIP-3 expression in the mitochondria and cytoplasmic AIF/Endo G translocation to the nucleus. BNIP-3 silencing significantly prevented AIF and Endo G translocation and decreased the apoptosis rate, cyt c release, and caspase-9 and caspase-3 activation. These results suggest that BNIP-3 is involved in the caspase-independent apoptotic pathway and is located upstream of AIF/Endo G; both the caspase-dependent and caspase-independent pathways are involved in cadmium-induced rPT cell apoptosis and act synergistically.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Zearalenone, which is ubiquitous in grains and animal feed, is a mycotoxin that can cause serious damage to animals and humans. Sertoli cells (SCs) can be used to study ZEA male reproductive toxicity ...in vitro. SCs provide energy for germ cells, where AMPK regulates intracellular energy. In order to explore the regulatory effect of AMPK on ZEA-induced lactate decline, we activated AMPK by AICAR and then inhibited AMPK by Compound C with ZEA-treated SCs for 24 h to detect intracellular lactate production-related indicators. Cell viability in the presence of 20 μmol/L ZEA and either 50 μmol/L AICAR or 5 μmol/L Compound C, respectively, did not damage SCs, and could effectively either activate or inhibit AMPK. Inhibition of AMPK promoted the production of pyruvate and lactate via increased expression of the glycolysis-related genes Pgam1 and the lactate production-related proteins GLUT1, LDHA, and MCT4. Activating AMPK inhibited the production of lactate and pyruvate by suppressing the expression of glycolysis-related genes HK1, Pgam1, and Gpi1 and that of lactate production-related proteins LDHA and MCT4. Zearalenone destroys the energy balance in SCs, activates P-AMPK, which inhibit the production of lactate and pyruvate in SCs. This also leads to the decrease of energy supply of SCs to spermatogenic cells, damages to reproductive system.
•Zearalenone interferes with the energy level of Sertoli cells and reduces lactate production.•Activated AMPK suppresses the production of lactate and pyruvate in Sertoli cells.•Activated AMPK suppresses Zearalenone-induced, glycolytic gene expression.•Activated AMPK suppresses Zearalenone-induced, lactate production-related proteins.
We present data and analysis of a set of balloon‐borne sounding profiles, which includes co‐located O3, CO, CH4, and particles, over the northern Tibetan Plateau during an Asian summer monsoon (ASM) ...season. These novel measurements shed light on the ASM transport behavior near the northern edge of the anticyclone. Joint analyses of these species with the temperature and wind profiles and supported by back trajectory modeling identify three distinct transport processes that dominate the vertical chemical structure in the middle troposphere, upper troposphere (UT), and the tropopause region. The correlated changes in profile structures in the middle troposphere highlight the influence of the strong westerly jet. Elevated constituent concentrations in the UT identify the main level of convective transport at the upstream source regions. Observed higher altitude maxima for CH4 characterize the airmasses' continued ascent following convection. These data complement constituent observations from other parts of the ASM anticyclone.
Plain Language Summary
Asian summer monsoon deep convection transports surface pollutants to the stratosphere. Although satellite data have provided clear evidence of this transport, in situ measurements are critical for characterizing how monsoon is vertically re‐distributing the regional emissions. We report new balloon‐borne measurements over the Tibetan Plateau that provide a unique data set on the northern edge of the anticyclone, complementing other observations.
Key Points
A novel set of in‐situ profile measurements of O3, CO, CH4 and particles from Tibetan Plateau during Asian summer monsoon are presented
Joint analyses of the profiles provide insights into transport processes controlling the northern edge of the Asian monsoon anticyclone
Observed CO profile maxima at 13–14 km (∼360–370 K) identify the level of convective transport at the upstream source regions
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