Project description:Cells labelled with the TPH1-venus fluorescent protein were sorted and collected for peptidomics analysis. Cells that were TPH1 negative were also collected and analysed.
Project description:Tryptophan hydroxylase 1 (TPH1), the rate-limiting enzyme in peripheral serotonin biosynthesis, has emerged as a critical driver of neuroendocrine prostate cancer (NEPC) progression. Elevated TPH1 expression is observed in NEPC cell lines and patient tumor samples. To elucidate the role of TPH1 in prostate cancer development and progression, we performed RNA sequencing (RNA-seq) in prostate cancer cells with either TPH1 knockdown or overexpression, compared to respective control cells. Differential gene expression analysis and subsequent pathway enrichment revealed key molecular programs regulated by TPH1. Functionally, TPH1 overexpression promotes tumor cell proliferation and the acquisition of neuroendocrine features, while genetic or pharmacological inhibition of TPH1 suppresses NEPC cell growth and neuroendocrine marker expression. These findings underscore the oncogenic role of TPH1 in NEPC and support its potential as a therapeutic target.
Project description:Reducing circulating serotonin by inhibition of Tph1 increases the sensitivity of BAT cells and this drives thermogenesis by fat and glucose oxidation. Here we report Insulin sensitivity changes by regulating Serotonin on skeletal muscle. Improved glucose tolerance and insulin sensitivity in HFD Tph1 KO mice. Inhibiting Tph1 increases AMPK activity, glucose uptake, myofiber size and decreases lipid droplet accumulation in HFD mice skeletal muscle. Inhibiting Tph1 in muscle showed activation of SIRT1/LKB1/AMPK pathway in skeletal muscle cells and increased p-ACC. Theses results indicates that protected insulin resistance and myosteatosis on skeletal muscle by lack of Serotonin by Tph1 on skeletal muscle.
Project description:It is known that reducing circulating serotonin by inhibiting Tph1 increases the sensitivity of BAT cells and this drives thermogenesis by fat and glucose oxidation. In our results inhibiting Tph1 in muscle showed activation of SIRT1/LKB1/AMPK pathway in skeletal muscle cells and increased p-ACC. Also, it's known that inhibiting adipose Htr2b signaling ameliorates HFD-induced systemic insulin resistance. Here we report insulin sensitivity changes by regulating serotonin in skeletal muscle by Htr2b. Inhibiting Htr2b increases AMPK activity, glucose uptake, and myofiber size and decreases lipid droplet accumulation in HFD mice skeletal muscle. These results indicate improved insulin resistance and myosteatosis in skeletal muscle by lack of Serotonin by Tph1/Htr2b on skeletal muscle.