Dataset Information

Subchronic arsenism-induced oxidative stress and inflammation contribute to apoptosis through mitochondrial and death receptor dependent pathways in chicken immune organs.

ABSTRACT: In many organ dysfunctions, arsenic and its compounds are well known to induce apoptosis by the mitochondria and death receptor apoptotic pathways in liver and airway. However, it is less reported that which signaling pathways contribute to excessive apoptosis of chicken immune organs, a major target of toxic metals biotransformation, which suffer from subchronic arsenism. In this study, we investigated whether the mitochondria or death receptor apoptotic pathways activated in the immune organs (spleen, thymus and bursa of Fabricius) of one-day-old male Hy-line chickens exposed to arsenic trioxide (As2O3), which were fed on diets supplemented with 0, 0.625, 1.25 and 2.5 mg/kg BW of As2O3 for 30, 60 and 90 days. We found that (1) Oxidative damage and inflammatory response were confirmed in the immune organs of chickens fed on As2O3 diet. (2) Subchronic arsenism induced typical apoptotic changes in ultrastructure. (3) TdT-mediated dUTP Nick-End Labeling (TUNEL) showed that the number of apoptotic cells significantly increased under subchronic arsenism. (4) As2O3-induced apoptosis of immune organs involved in mitochondrial pathway (decrease of B-cell lymphoma-2 (Bcl-2) and increase of protein 53 (p53), Bcl-2 Associated X Protein (Bax), caspase-9, caspase-3) and death receptor pathway (increase of factor associated suicide (Fas) and caspase-8). In conclusion, this work is the first to demonstrate that the activation of mitochondria and death receptor apoptosis pathways can lead to excessive apoptosis in immune organs of chickens, which suffer from subchronic arsenism, meanwhile, oxidative stress as well as subsequent inflammatory is a crucial driver of apoptosis.

SUBMITTER: Zhao H

PROVIDER: S-EPMC5522337 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Subchronic arsenism-induced oxidative stress and inflammation contribute to apoptosis through mitochondrial and death receptor dependent pathways in chicken immune organs.

Zhao Hongjing H He Ying Y Li Siwen S Sun Xiao X Wang Yu Y Shao Yizhi Y Hou Zhijun Z Xing Mingwei M

Oncotarget 20170601 25

In many organ dysfunctions, arsenic and its compounds are well known to induce apoptosis by the mitochondria and death receptor apoptotic pathways in liver and airway. However, it is less reported that which signaling pathways contribute to excessive apoptosis of chicken immune organs, a major target of toxic metals biotransformation, which suffer from subchronic arsenism. In this study, we investigated whether the mitochondria or death receptor apoptotic pathways activated in the immune organs ...[more]

PMID: 28454103

Similar Datasets

Project description:Weaning is associated with increased occurrence of infections and diseases in piglets. Recent findings indicate that weaning induces mitochondrial dysfunction and oxidative stress conditions that more severely impact smaller piglets. The objective of this study was to characterize the molecular mechanisms underlying these physiological consequences and the relation with systemic inflammatory status in both normal and low birth weight (NBW and LBW) piglets throughout the peri-weaning period. To conduct the study, 30 sows were inseminated, and specific piglets from their litters were assigned to one of two experimental groups: NBW (n = 60, 1.73 ± 0.01 kg,) and LBW piglets weighing less than 1.2 kg (n = 60, 1.01 ± 0.01 kg). Then, 10 piglets from each group were selected at 14, 21 (weaning), 23, 25, 29 and 35 days of age to collect organ and plasma samples. Specific porcine RT2 Profiler™ PCR Arrays related to mitochondrial function, oxidative stress, inflammation and apoptosis processes were first used to target genes that are modulated after weaning in NBW piglets (d 23 and d 35 vs. d 14). Expression of selected genes was evaluated by quantitative PCR. These analyses revealed that expression of inflammatory genes CXCL10 and CCL19 increased after weaning in intestinal mucosa, while expression of genes encoding subunits of the mitochondrial respiratory chain was downregulated in liver and kidney of both groups. Interestingly, major modulators of mitophagy (BNIP3), cell survival (BCL2A1) and antioxidant defense system (TXNRD2, GPx3, HMOX1) were found to be highly expressed in NBW piglets. The systemic levels of TNF-α and IL1-β significantly increased following weaning and were higher in NBW piglets. These results provide novel information about the molecular origin of mitochondrial dysfunction and oxidative stress observed in weaned piglets and suggest that clearance of dysfunctional mitochondria, antioxidant defenses and inflammatory response are compromised in LBW piglets.

Project description:Lipopolysaccharide (LPS) is a known inducer of inflammatory signaling which triggers generation of reactive oxygen species (ROS) and cell death in responsive cells like THP-1 promonocytes and freshly isolated human monocytes. A key LPS-responsive metabolic pivot point is the 9.5 megadalton mitochondrial pyruvate dehydrogenase complex (PDC), which provides pyruvate dehydrogenase (E1), lipoamide-linked transacetylase (E2) and lipoamide dehydrogenase (E3) activities to produce acetyl-CoA from pyruvate. While phosphorylation-dependent decreases in PDC activity following LPS treatment or sepsis have been deeply investigated, redox-linked processes have received less attention. Data presented here demonstrate that LPS-induced reversible oxidation within PDC occurs in PDCE2 in both THP-1 cells and primary monocytes. Knockout of PDCE2 by CRISPR and expression of FLAG-tagged PDCE2 in THP-1 cells demonstrated that LPS-induced glutathionylation is associated with wild type PDCE2 but not mutant protein lacking the lipoamide-linking lysine residues. Moreover, the mitochondrially-targeted electrophile MitoCDNB elevates ROS similar to LPS but does not cause PDCE2 glutathionylation. However, both LPS and MitoCDNB together are synergistic for PDCE2 glutathionylation, ROS production, and cell death. These results suggest that glutathionylation on PDCE2 lipoamide sulfurs is a specific modification associated with LPS and cell death which is not recapitulated by a general rise in mitochondrial ROS, but is enhanced after LPS treatment by rising oxidative stress exerted by MitoCDNB that impairs reductase systems.HighlightsPDCE2 is oxidized and glutathionylated (-SSG) during acute inflammation in monocytesPDCE2 knockout cells exhibit decreased ROS production during acute inflammationLipopolysaccharide-induced PDCE2-SSG occurs in THP1 cells and fresh monocytesLipoamide-deficient PDCE2 exhibits lower LPS-induced PDCE2-SSG and ROS productionMitoCDNB leads to ROS production but not PDCE2-SSG, but is synergistic with LPS.

Dataset Information

Subchronic arsenism-induced oxidative stress and inflammation contribute to apoptosis through mitochondrial and death receptor dependent pathways in chicken immune organs.

Publications

Subchronic arsenism-induced oxidative stress and inflammation contribute to apoptosis through mitochondrial and death receptor dependent pathways in chicken immune organs.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets