Role of selenoprotein M knockdown in the melatonin antagonism of nickel-induced apoptosis and endoplasmic reticulum stress in mouse heart

The aim of this study was to investigate the role of selenoprotein M(SelM)in endoplasmic reticulum stress and apoptosis in nickel-exposed mouse hearts and to explore the detoxifying effects of melatonin.At 21 d after intraperitoneal injection of nickel chloride(NiCl_(2))and/or melatonin into male wild-type(WT)and SelM knockout(KO)C57BL/6J mice,NiCl_(2)was found to induce changes in the microstructure and ultrastructure of the hearts of both WT and SelM KO mice,which were caused by oxidative stress,endoplasmic reticulum stress,and apoptosis,as evidenced by decreases in malondialdehyde(MDA)content and total antioxidant capacity(T-AOC)activity.Changes in the messenger RNA(mRNA)and protein expression of genes related to endoplasmic reticulum stress(activating transcription factor 4(ATF4),inositol-requiring protein 1(IRE1),c-Jun N-terminal kinase(JNK),and C/EBP homologous protein(CHOP))and apoptosis(B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),Caspase-3,Caspase-9,and Caspase-12)were also observed.Notably,the observed damage was worse in SelM KO mice.Furthermore,melatonin alleviated the heart injury caused by NiCl_(2)in WT mice but could not exert a good protective effect in the heart of SelM KO mice.Overall,the findings suggested that the antioxidant capacity of SelM,as well as its modulation of endoplasmic reticulum stress and apoptosis,plays important roles in nickel-induced heart injury.

Prenatal cadmium exposure impairs neural tube closure via inducing excessive apoptosis in neuroepithelium

Birth defects have become a public health concern.The hazardous environmental factors exposure to embryos could increase the risk of birth defects.Cadmium,a toxic environmental factor,can cross the placental barrier during pregnancy.Pregnant woman may be subjected to cadmium before taking precautionary protective actions.However,the link between birth defects and cadmium remains obscure.Cadmium exposure can induce excessive apoptosis in neuroepithelium during embryonic development progresses.Cadmium exposure activated the p53 via enhancing the adenosine 5‘-monophosphate(AMP)-activated protein kinase(AMPK)and reactive oxygen species'(ROS)level.And cadmium decreases the level of Paired box 3(Pax3)and murine double minute 2(Mdm2),disrupting the process of p53 ubiquitylation.And p53 accumulation induced excessive apoptosis in neuroepithelium during embryonic development progresses.Excessive apoptosis led to the failure of neural tube closure.The study emphasizes that environmental materials may increase the health risk for embryos.Cadmium caused the failure of neural tube closure during early embryotic day.Pregnant women may be exposed by cadmium before taking precautionary protective actions,because of cadmium concentration-containing foods and environmental tobacco smoking.This suggests that prenatal cadmium exposure is a threatening risk factor for birth defects.

Calcium overload and reactive oxygen species accumulation induced by selenium deficiency promote autophagy in swine small intestine

Selenium(Se)deficiency can seriously affect the small intestine of swine,and cause diarrhea in swine.However,the specific mechanism of Se deficiency-induced swine diarrhea has rarely been reported.Here,to explore the damage of Se deficiency on the calcium homeostasis and autophagy mechanism of swine,in vivo and in vitro models of swine intestinal Se deficiency were established.Twenty-four pure line castrated male Yorkshire pigs(45 d old,12.50±1.32 kg,12 full-sibling pairs)were divided into 2 equal groups and fed Se-deficient diet(0.007 mg Se/kg)as the Se-deficiency group,or fed Se-adequate diet(0.3 mg Se/kg)as the control group for 16 weeks.The intestinal porcine enterocyte cell line(IPEC-J2)was divided into 2 groups,and cultured by Se-deficient medium as the Se-deficient group,or cultured by normal medium as the control group.Morphological observations showed that compared with the control group,intestinal cells in the Se-deficiency group were significantly damaged,and autophagosomes increased.Autophagy staining and cytoplasmic calcium staining results showed that in the Sedeficiency group,autophagy increased and calcium homeostasis was destroyed.According to the reactive oxygen species(ROS)staining results,the percentage of ROS in the Se-deficiency group was higher than that in the control group in the in vitro model.Compared with the control group,the protein and mRNA expressions of autophagy-calcium-related genes including Beclin 1,microtubule-associated proteins 1 A(LC3-1),microtubule-associated proteins 1 B(LC3-2),autophagy-related protein 5(ATG5),autophagy-related protein 12(ATG12),autophagy-related protein 16(ATG16),mammalian target of rapamycin(mTOR),calmodulin-dependent protein kinase kinaseβ(CAMKK-β),adenosine 5’-monophosphate-activated protein kinase(AMPK),sarco(endo)plasmic reticulum Ca2+-ATPase(SERCA),and calpain in the Se-deficiency group were significantly increased which was consistent in vivo and in vitro(P<0.05).Altogether,our results indicated that Se deficiency could destroy the calcium homeostasis of the swine small intestine to trigger cell autophagy and oxidative stress,which was helpful to explain the mechanism of Se deficiency-induced diarrhea in swine.

Nano-selenium alleviates cadmium-induced cerebellar injury by activating metal regulatory transcription factor 1 mediated metal response

This study aims to investigate the role of metal regulatory transcription factor 1(MTF1)-mediated metal response in cadmium(Cd)-induced cerebellar injury,and to evaluate the antagonistic effects of nanoselenium(Nano-Se)against Cd toxicity.A total of 80 chicks(1 d old,male,Hy-Line Variety White)were randomly allocated to 4 treatment groups for 3 months:the control group(fed with a basic diet,n=20),the Nano-Se group(basic diet with 1 mg/kg nano-Se 1 mg/kg Nano-Se in basic diet,n=20),the NanoSe+Cd group(basic diet with 1 mg/kg Nano-Se and 140 mg/kg Cd Cl_(2),n=20)and the Cd group(basic diet with 140 mg/kg Cd Cl_(2),n=20).The results of the experiment showed that the Purkinje cells were significantly decreased with their degradation and indistinct nucleoli after Cd exposure.Moreover,exposure to Cd caused a significant accumulation of Cd and cupper.However,the contents of Se,iron,and zinc were decreased,thereby disturbing the metal homeostasis in the cerebellum.The Cd exposure also resulted in high levels of malondialdehyde(MDA)and down regulation of selenoprotein transcriptome.Furthermore,the expressions of MTF1,metallothionein 1(MT1),MT2,zinc transporter 3(ZNT3),ZNT5,ZNT10,zrt,irt-like protein 8(ZIP8),ZIP10,transferrin(TF),ferroportin 1(FPN1),ATPase copper transporting beta(ATP7B),and copper uptake protein 1(CTR1)were inhibited by Cd exposure.However,all these changes were significantly alleviated by the supplementation of Nano-Se.This study proved that Cd could disorder metal homeostasis and induce oxidative stress,whereas Nano-Se could relieve all these negative effects caused by Cd via activating the MTF1-mediated metal response in the cerebellum of chicken.