Mammalian members of the proton-coupled oligopeptide transporter family are integral membrane proteins that mediate the cellular uptake of di/tripeptides and peptide-like drugs and couple substrate translocation to the movement of H , with the transmembrane electrochemical proton gradient providing the driving force. Peptide transporters are responsible for the (re)absorption of dietary and/or bacterial di- and tripeptides in the intestine and kidney and maintaining homeostasis of neuropeptides in the brain. These proteins additionally contribute to absorption of a number of pharmacologically important compounds. In this overview article, we have provided updated information on the structure, function, expression, localization, and activities of PepT1 (SLC15A1), PepT2 (SLC15A2), PhT1 (SLC15A4), and PhT2 (SLC15A3). Peptide transporters, in particular, PepT1 are discussed as drug-delivery systems in addition to their implications in health and disease. Particular emphasis has been placed on the involvement of PepT1 in the physiopathology of the gastrointestinal tract, specifically, its role in inflammatory bowel diseases. © 2018 American Physiological Society. Compr Physiol 8:731-760, 2018.

Neuroinflammation can be induced under several conditions including pathogen infection such as virus. As the main immune cells in brain, microglia activation plays a pivotal role in neuroinflammation by responding to the invading pathogens (viral DNA/RNA) through toll-like receptors. Chronic activation of microglia caused by sustained viral infection will lead to persistent release of pro-inflammatory molecules, which is different from their beneficial functions under physiological conditions. Sustained exposure of neurons to the inflammatory condition can result in neuronal dysfunction as well as cell degeneration that contribute to the pathogenesis of several neurological disorders. This review proposed that during sustained infection, viral DNA/RNA activated microglia through TLRs, inducing persistent inflammatory response that causes long term, mild but irreversible changes, which ultimately contribute to the neuronal dysfunction or cell degeneration.

Gut barrier dysfunction can result in the liver being exposed to an elevated level of gut-derived bacterial products via portal circulation. Growing evidence suggests that systemic exposure to these bacterial products promotes liver diseases including hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). However, prospective studies have not examined the association between biomarkers of gut barrier dysfunction and HCC risk in a population of hepatitis B or C viral (HBV/HCV) carriers. We investigated whether prediagnostic, circulating biomarkers of gut barrier dysfunction were associated with HCC risk, using the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer (REVEAL)-HBV and REVEAL-HCV cohorts from Taiwan. REVEAL-HBV included 185 cases and 161 matched controls, and REVEAL-HCV 96 cases and 96 matched controls. The biomarkers quantitated were immunoglobulin A (IgA), IgG, and IgM against lipopolysaccharide (LPS) and flagellin, soluble CD14 (an LPS coreceptor), and LPS-binding protein (LBP). Odds ratios (ORs) and 95% confidence intervals (CIs) for associations between biomarker levels and HCC were calculated using multivariable-adjusted logistic regression.

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Circular dichroism and dye leakage assays revealed that the amidated Cterminus maintains better peptide structural stability and ability to disrupt membranes than the carboxylic form. Similarly, 31 P and 2 H solid-state NMR displayed that the C-terminal amidated peptide had a stronger interaction with the phospholipid headgroups and a slight effect on the lipid acyl chains. Cell viability and antibacterial assays showed that the amidated C-terminus induced greater antibacterial and cytotoxic effect while the carboxylic C-terminus promoted mild cytotoxic effect and reduced antibacterial efficacy. Overall, the results showed that the C-terminus of maculatin is critical in modulating the peptide mode of action.