Crosstalk between Mfn2-mediated mitochondria associated membranes disorder and autophagy induced by molybdenum and cadmium in sheep heart.

To investigate the crosstalk of mitochondria associated membranes (MAMs) disorder and autophagy co-induced by molybdenum (Mo) and cadmium (Cd) in sheep hearts. A total of 48 sheep were randomly divided into 4 groups: control group, Mo group, Cd group and Mo + Cd group. The intragastric administration lasted for 50 days. The results showed that Mo or/and Cd exposure could cause morphological damage, imbalance of trace elements and antioxidant function, Ca2+ concentration decreased markedly, and significantly increase the contents of Mo or/and Cd in myocardium. Additionally, the mRNA and protein levels of endoplasmic reticulum stress (ERS) related factors and mitochondrial biogenesis related factors were altered by Mo or/and Cd, as well as the content of ATP, inducing ERS and mitochondrial dysfunction. Meanwhile, Mo or/and Cd could lead to the alteration of expression level of MAMs-related genes and proteins, and the distance between mitochondria and endoplasmic reticulum (ER), resulting in MAMs disorder. Moreover, Mo or/and Cd exposure upregulated the mRNA and protein levels of autophagy related factors. In conclusion, our results revealed that Mo or/and Cd exposure caused ERS, mitochondrial dysfunction and structural MAMs disruption, ultimately leading to autophagy in sheep hearts, and the effects of Mo and Cd co-exposure were more obvious.

Selenium alleviates cadmium-induced aging via mitochondrial quality control in the livers of sheep.

Cadmium (Cd) is a heavy metal with toxicity that induces mitochondrial dysfunction and aging, and selenium (Se) can alleviate its toxicity. However, the underlying mechanism of Se alleviating Cd-induced aging in sheep livers deserves further study. This study was to explore the protective mechanism of Se on the Cd-induced aging in the livers of sheep. A total of forty-eight sheep weighing about 10 kg were randomly divided into four groups: control group, Se group [0.34 mg Se·kg-1·body weight (BW)], Cd group (1 mg Cd·kg-1·BW), and Se + Cd group (0.34 mg Se·kg-1·BW +1 mg Cd·kg-1·BW). The results showed that Cd caused vacuolization, granule denaturation, and mitochondrial vacuolization in hepatocytes. Furthermore, the levels of catalase (CAT), total superoxide dismutase (T-SOD), glutathione (GSH) and adenosine triphosphate (ATP) in liver mitochondria were down-regulated, but the levels of hydrogen peroxide (H2O2) and malonaldehyde (MDA) were up-regulated under Cd treatment. Besides, the cyclin-dependent kinase inhibitor 1 (P21) immunohistochemistry positive signal and the puncta of immunofluorescence co-locations of E3 ubiquitin ligase Parkin (Parkin)/ cytochrome c oxidase IV (COX IV) and light chain 3B (LC3B)/COX IV were increased under Cd stress. Moreover, Cd exposure decreased the levels of mitochondrial biogenesis and fusion related factors and minichromosome maintenance protein 2 (MCM2), but increased the levels of mitochondrial fission, mitophagy, and cell aging related factors. However, the variations mentioned above caused by Cd were effectively ameliorated by Se co-treatment. In conclusion, Se might alleviate Cd-induced aging via regulating mitochondrial quality control in sheep livers.

Compound probiotics alleviate cadmium-induced intestinal dysfunction and microbiota disorders in broilers.

Cadmium (Cd), a common environmental pollutant, seriously threatens the health of intestine. This research aimed to investigate the effects of compound probiotics (CP) on intestinal dysfunction and cecal microbiota dysregulation induced by Cd in broilers. A total of 240 1-day-old Arbor Acre (AA) broilers were randomly assigned to four groups. After 120 days of feeding, the jejunum tissues and cecal contents were sampled for jejunum histopathological observation, the intestinal barrier and inflammatory factors related mRNA and proteins examinations, and intestinal microbiota analysis. The results showed that Cd could cause jejunal villus damage and inflammatory cells infiltration, down-regulate the mRNA levels of intestinal barrier related genes (ZO-1, ZO-2, ZO-3, Claudin1, Claudin3, Claudin4, Occludin, and E-cadherin) and inflammatory factor related genes (IL-1ß, IL-18, IFN-γ, NF-κB), and the protein levels of Claudin1, ZO-1, Occludin, but up-regulate the Claudin2, IL-2, IL-4 and IL-10 mRNA levels. However, the addition of CP could effectively improve these changes. In addition, 16S rRNA gene sequencing analysis showed that compared with the Cd group, supplementation CP increased the abundance of Lactobacillales, Clostridiales, Firmicutes, together with regulations on the pathways responsible for energy metabolism, translation and amino acid metabolism. In conclusion, CP could improve intestinal barrier damage and intestinal microbiota disturbance induced by Cd.

Molybdenum and Cadmium Co-induce Mitochondrial Quality Control Disorder via FUNDC1-Mediated Mitophagy in Sheep Kidney.

Molybdenum (Mo), fundamental trace mineral for animals and plants, but undue Mo damages animal health. Cadmium (Cd) is a toxic heavy metal that exists in the environment. Nevertheless, the mechanism of Mo and Cd on mitochondrial quality control are still indistinct. The objective of this research was to explore the effects of mitophagy on mitochondrial quality control via the FUNDC1-mediated by Mo and Cd in sheep kidney. Forty-eight 2-month-old sheep were stochastically divided into four groups, as shown below: control group, Mo [45 mg/kg body weight (BW)] group, Cd (1 mg/kg BW) group and Mo (45 mg/kg BW)+Cd (1 mg/kg BW) group, with 50 days feed technique. The results showed that Mo or/and Cd attract an unbalance of trace minerals and vacuoles and granular degeneration of renal tubular epithelial cells, and increase the number of mitophagosomes and vacuole-mitochondria and LC3 puncta and MDA and H2O2 contents, and decrease ATP content in the kidney. Moreover, Mo or/and Cd treatment could upregulate the mRNA levels of FUNDC1, LC3A, LC3B, PGAM5, DRP1, FIS1 and MFF, and the protein levels of FUNDC1, p-FUNDC1, LC3II/LC3I, DRP1, MFF and FIS1, downregulate the mRNA levels of MFN1, MFN2, OPA1, PGC-1α, SIRT1, SIRT3, FOXO1 and FOXO3, and the protein levels of MFN1, MFN2, OPA1 and PGC-1α. Notably, variations of above-mentioned factors in Mo and Cd group were more obvious than in Mo or Cd groups. Taken together, these results displayed that Mo and Cd co-treatment might induce mitochondrial quality control disorder via FUNDC1-mediated mitophagy in sheep kidney.