Stimulation of β-adrenergic receptors activates type I and II cyclic AMP–dependent protein kinase A, resulting in phosphorylation of various proteins in the heart. It has been proposed that PKA II compartmentalization by A-kinase–anchoring proteins (AKAPs) regulates cyclic AMP–dependent signaling in the cell. We investigated the expression and localization of AKAP100 in adult hearts. By immunoblotting, we identified AKAP100 in adult rat and human hearts, and showed that type I and II regulatory (RI and II) subunits of PKA are present in the rat heart. By immunofluorescence and confocal microscopy of rat cardiac myocytes and cryostat sections of rat left ventricle papillary muscles, we localized AKAP100 to the nucleus, sarcolemma, intercalated disc, and at the level of the Z-line. After double immunostaining of transverse cross-sections of the papillary muscles with AKAP100 plus α-actinin–specific antibodies or AKAP100 plus ryanodine receptor–specific antibodies, confocal images showed AKAP100 localization at the region of the transverse tubule/junctional sarcoplasmic reticulum. RI is distributed differently from RII in the myocytes. RII, but not RI, was colocalized with AKAP100 in the rat heart. Our studies suggest that AKAP100 tethers PKA II to multiple subcellular compartments for phosphorylation of different pools of substrate proteins in the heart.

Host defense peptides (HDPs) are efficient defense components of the innate immune system, playing critical roles in intestinal homeostasis and protection against pathogens. This study aims to investigate the interference effects of DON on the intestinal porcine HDPs expression in piglets and intestinal porcine epithelial cell line (IPEC-J2) cells, and elucidate the underlying mechanisms through which it functions. In an animal experiment, intestinal HDPs were determined in weaned piglets fed control and 1.28 mg/kg or 2.89 mg/kg DON-contaminated diets. Dietary exposure to DON significantly decreased piglet average daily gain, increased intestinal permeability and depressed the expression of porcine β-defensin1 (pBD1), pBD2, pBD3, epididymis protein 2 splicing variant C (pEP2C), PMAP23, and proline/arginine-rich peptide of 39 amino acids (PR39) in the intestine (p < 0.05). In IPEC-J2 cells, DON decreased cell viability and inhibited the expression of pBD1, pBD3, pEP2C, PG1-5, and PR39 (p < 0.05). NOD2, key regulator that is responsible for HDPs production, was markedly downregulated, whereas caspase-12 was activated in the presence of DON. In conclusion, DON induced caspase-12 activation and inhibited the NOD2-mediated HDPs production, which led to an impaired intestinal barrier integrity of weaned piglets. Our study provides a promising target for future therapeutic strategies to prevent the adverse effects of DON.

This study investigated the potential link between gut microbiota and deoxynivalenol (DON)-induced feed refusal. A total of 24 barrows were randomly divided into one of three diets containing 0.61 (control diet), 1.28, or 2.89 mg DON/kg feed for 28 days. Dietary exposure to DON at 2.89 mg/kg significantly decreased the relative abundances of unclassified_f_Lachnospiraceae, Phascolarctobacterium and Ruminococcaceae_UCG-014, whereas it increased Prevotella_9 and norank_f_Prevotellaceae in the cecal digesta. Moreover, the decreased relative abundance of unclassified_f_Lachnospiraceae induced by DON exposure was positively correlated with average daily feed intake. Exposure to DON increased the serum concentrations of glucagon-like peptide-1 and peptide YY but reduced the levels of serum growth hormone and insulin-like growth factor 1. In summary, these findings suggest that chronic dietary exposure to DON induces disturbances of intestinal microbiota. Disturbed appetite-regulating hormones and somatotropic-axis-hormone secretion induced by negative microbial changes could be the potential mechanisms for DON-induced anorexia.

This study aims to determine whether sodium butyrate (SB) could antagonize deoxynivalenol (DON)-induced intestinal epithelial dysfunction. In a four-week feeding trial, twenty-eight barrows were randomly divided into four treatments: (1) uncontaminated basal diet (control); (2) 4 mg/kg DON-contaminated diet (DON); (3) basal diet supplemented with 0.2% SB (SB); and (4) 4 mg/kg DON + 0.2% SB (DON + SB). A decrease in performance was observed in DON-exposed animals, which was prevented by the dietary SB supplementation. DON exposure also depressed the expression of host defense peptides (HDPs) in the intestine, impaired the intestinal barrier integrity, and disturbed the gut microbiota homeostasis. These alterations induced by DON were attenuated by SB supplementation. The supplementation of 0.2% SB ameliorated the adverse effects of DON on the liver in terms of hepatic lesions as well as serum concentrations of alkaline phosphatase and aspartate aminotransferase. In IPEC-J2 cells, pretreatment with SB alleviated the DON-induced decreased cell viability. Additionally, the NOD2/caspase-12 pathway participated in the alleviation of SB on DON-induced diminished HDP expression. Taken together, these data demonstrated that SB protected piglets from DON-induced intestinal barrier dysfunction potentially through stimulation of intestinal HDP assembly and regulation in gut microbiota.