The mammalian ste20 kinase (MST) signaling pathway plays an important role in the regulation of apoptosis and cell cycle control. We sought to understand the role of MST2 kinase and Salvador homolog 1 (SAV1), a scaffolding protein that functions in the MST pathway, in adipocyte differentiation. MST2 and MST1 stimulated the binding of SAV1 to peroxisome proliferator-activated receptor γ (PPARγ), a transcription factor that plays a key role in adipogenesis. The interaction of endogenous SAV1 and PPARγ was detected in differentiating 3T3-L1 adipocytes. This binding required the kinase activity of MST2 and was mediated by the WW domains of SAV1 and the PPYY motif of PPARγ. Overexpression of MST2 and SAV1 increased PPARγ levels by stabilizing the protein, and the knockdown of SAV1 resulted in a decrease of endogenous PPARγ protein in 3T3-L1 adipocytes. During the differentiation of 3T3-L1 cells into adipocytes, MST2 and SAV1 expression began to increase at 2 days when PPARγ expression also begins to increase. MST2 and SAV1 significantly increased PPARγ transactivation, and SAV1 was shown to be required for the activation of PPARγ by rosiglitazone. Finally, differentiation of 3T3-L1 cells was augmented by MST2 and SAV1 expression and inhibited by knockdown of MST1/2 or SAV1. These results suggest that PPARγ activation by the MST signaling pathway may be a novel regulatory mechanism of adipogenesis.

The mammalian ste20-like kinase (MST) pathway is important in the regulation of apoptosis and cell cycle and emerges as a novel tumor suppressor pathway. MST-induced phosphorylation of Salvador homolog 1 (SAV1), which is a scaffold protein, has not been evaluated in detail. We performed a mass spectrometric analysis of the SAV1 protein that was co-expressed with MST2. Phosphorylation was detected at Thr-26, Ser-27, Ser-36 and Ser-269. Although single or double mutations had little effects, the mutation of all four residues in SAV1 to Ala (SAV1-4A) had inhibitory effects on the MST pathway. MST2-mediated induction of SAV1-4A protein levels, SAV1-4A interaction with MST2 and the self-dimerization of SAV1-4A were weaker compared to those of wild-type SAV1. SAV1-4A inhibited MST2-and K-RasG12V-induced cell death of MCF7 cells. These results suggest that MST-mediated phosphorylation of four residues within SAV1 may be important in the induction of cell death by the MST pathway. [BMB reports 2011; 44(9): 584-589]

Lactococcus lactis subsp. cremoris is a lactic acid bacterium commonly used in the cheese manufacturing industry. It is known to produce antibacterial peptides and has recently received attention for its role as a probiotic strain. Here, we report the isolation of a new strain, Lactococcus lactis subsp. cremoris RPG-HL-0136 (RPG0136) from dried compost, which exhibits strong antibacterial activity. When RPG0136 was fed to mice, it increased the intestinal population of two beneficial bacteria, Lactobacillus and Bifidobacterium, whereas it decreased the intestinal population of two harmful bacteria, Bacteroides and Enterobacter. In addition, it increased the concentration of short-chain fatty acids, including acetic acid, propionic acid, and butyric acid, with a simultaneous decrease in pH, and accelerated the catabolic degradation of proteins, lipids, and starch. Lastly, RPG0136 increased the plasma IgG and intestinal mucosal SIgA concentrations and upregulated Reg3r, MUC1, and MUC2 expression to improve the intestinal mucosal immune function. The results of this study suggest that RPG0136 is a potential probiotic strain that supports the growth of a beneficial microbiome by promoting the synthesis of organic acids and enhancing intestinal immune function.

Background Benzo(a)pyrene (BaP) is a carcinogenic compound in contaminated foodstuffs. The effect of oral intake of the environmental carcinogen BaP under low doses and frequent exposure on a digestive system has not been thoroughly verified. Methods In this regard, this study was conducted to prove the toxicity effects of BaP on the stomach and colon tissue after exposure to C57BL/6 mouse (3 and 6 µg/kg) following daily oral administration for 60 days. This study investigated acute gastric mucosal injury, severe gastric edema, cell infiltration, and mononuclear cells, multifocal cells, and tumoral inflammatory cells. Results The results of ELISA showed that the expression of serum interleukin (IL)-6 and tumor necrosis factor-α in the BaP exposure group were significantly increased, and a high level of DNA adduct distribution in their stomach and colon. Moreover, this study has confirmed the expression of early carcinogenesis markers: nuclear factor (NF)-κB, p53, IL-6, superoxide dismutase 1 (SOD1), mucin (MUC1 and MUC2), and β-catenin in the stomach and colon, and showed that there was a significant increase in IL-6, NF-κB, SOD1, β-catenin, and MUC1 ( P < 0.05). At the same time, there was a significant decrease in MUC2 and p53 ( P < 0.05). Thus, even in low doses, oral intake of BaP can induce DNA damage, increasing the potential risk of gastrointestinal cancer. Conclusion This study will provide a scientific basis for researching environmental contaminated food and intestinal health following daily oral administration of BaP.

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