Transcriptome analysis reveals that hydrogen sulfide exposure suppresses cell proliferation and induces apoptosis through ciR-PTPN23/miR-15a/E2F3 signaling in broiler thymus.

The immune organs, like thymus, are one of the targets of hydrogen sulfide (H2S). Previously we reported that H2S induced the differential expression of mRNAs that implicating apoptosis in thymus, however, the roles of noncoding RNAs (ncRNAs) in H2S-induced thymus injury are still unknown. Pollution gases could alter the expression of ncRNAs, which have been shown to play important roles in many physiological and pathophysiological processes, including immune activity. This study revealed that H2S exposure induced 9 differentially expressed circRNAs and 15 differentially expressed miRNAs in chicken thymus. Furthermore, the circRNA - miRNA - mRNA network was constructed. We discovered that circR-PTPN23 - miR-15a - E2F3 was involved in the cell cycle and apoptosis. Further, an in vitro H2S exposure model was established using HD11 cell line and demonstrated that H2S suppressed cell proliferation and induced apoptosis. Moreover, ciR-PTPN23 and E2F3 were downregulated, but miR-15a was upregulated in both the thymus and HD11 cell line after H2S exposure. Bioinformatics analysis revealed that ciR-PTPN23 directly bound to miR-15a and that E2F3 was the target gene of miR-15a. Knocking down ciR-PTPN23 suppressed HD11 proliferation and caused G1 arrest and apoptosis, however, this phenomenon could be partially reversed by ciR-PTPN23 overexpression or miR-15a silencing. In summary, the ciR-PTPN23 - miR-15a - E2F3 axis was involved in H2S-induced cell proliferation suppression and apoptosis.

Cadmium induces apoptosis of pig lymph nodes by regulating the PI3K/AKT/HIF-1α pathway.

OBJECTIVE: This study was aimed to explore the possible mechanism of environmental metal cadmium (Cd) inducing apoptosis of pig lymph nodes. METHOD: 10 healthy 6-week-old weaned piglets were randomly divided into two groups (n = 5 pigs/group). The control group was fed with a basic diet, and the test group was fed with a basic diet of 20 mg/kg CdCl2. RESULTS: The Cd deposition in mesenteric lymph nodes (MLN), inguinal lymph nodes (ILN) and submaxillary lymph nodes (SLN) after Cd exposure was 2.37 folds, 1.4 folds and 1.8 folds of the control group, respectively. And the rate of MLN and ILN apoptotic cells in the Cd group was 4.11 folds and 9.18 folds of the control group, respectively. The mRNA levels of SOD1, SOD2, CAT, GPX1 and GSH in the Cd group were reduced. Similarly, the two-phase detoxification enzymes had a significant downward trend. Cd exposure decreased the activities of GSH, GSH-Px, SOD, CAT, and increased H2O2 and MDA levels. The mRNA and protein levels of Drp1 and Mff in the Cd group were higher than the corresponding control group, and the mRNA and protein levels of Mfn1 and Mfn2 were lower than those in the control group. In addition, the mRNA and protein levels of pro-apoptotic genes in the Cd group were lower than those in the control group. Cd can significantly reduce the expression of PI3K, AKT and HIF-1α in the three lymph nodes. In summary, Cd induces oxidative stress and regulates the PI3K/AKT/HIF-1α signal transduction pathway to cause mitochondrial dynamics disorder, which leads to the apoptosis of pig lymph nodes, suggesting that Cd-induced mitochondrial pathway apoptosis is related to Cd pig lymph nodes play an important role in the toxicity mechanism.

MicroRNA-294 Regulates Apoptosis of the Porcine Cerebellum Caused by Selenium Deficiency via Targeting iNOS.

Deficiency of the essential trace element selenium (Se) can lead to cell apoptosis, and various microRNAs (miRNAs) are known to participate in the regulation of apoptosis by regulating their target genes. In this study, we explore the effect of Se deficiency on porcine cerebellar cell apoptosis and the role of miRNA in this process. After constructing a low-Se pig model, we observed the porcine cerebellum through an electron microscope and observed obvious characteristics of apoptosis. Moreover, it was found that the expression of miR-294 in Se-deficient pigs was significantly lower than that in the control group. Through bioinformatics, qRT-PCR, western blot analysis, and other experimental techniques, we further confirmed that inducible nitric oxide synthase (iNOS) is one of the target genes of miR-294. Our experimental results show that Se deficiency can reduce the expression of miR-294 and increase both the expression of iNOS and the nitric oxide (NO) content (P < 0.01). The expression of heat shock proteins (HSPs, such as HSP70, HSP90, HSP60, HSP40, and HSP27) and mitochondrial pathway-related indicators, such as Bcl2-associated X protein (Bax), cytochrome C (Cyt-C), and cysteinyl aspartate-specific proteinases (caspase 3, caspase 7, and caspase 8), was upregulated (P < 0.05), and the expression of B cell lymphoma-2 (Bcl-2) was downregulated (P < 0.05). In summary, we believe that Se deficiency can lead to abnormal expression of miR-294 and HSPs; moreover, the mitochondrial apoptosis pathway is activated, which significantly enhances apoptosis of cerebellar cells in Se-deficient pigs. These results enrich the biological effects of Se deficiency.