Glutamine is a key regulator for amino acid-controlled cell growth through the mTOR signaling pathway in rat intestinal epithelial cells

Abstract

Amino acids, especially branched-chain amino acids such as l-leucine, have been shown to regulate activation of p70 S6 kinase and phosphorylation of 4E-BP1 through the mTOR signaling pathway. In our recent study, l-arginine was also shown to activate the mTOR signaling pathway in rat intestinal epithelial cells. l-Glutamine is an amino acid that is required for culturing of numerous cell types, including rat intestinal epithelial cells. In this study, we showed that l-glutamine inhibited the activation of p70 S6 kinase and phosphorylation of 4E-BP1 induced by arginine or leucine in rat intestinal epithelial cells. Although the molecular mechanism of l-glutamine-induced inhibition of the mTOR signaling pathway is still unknown, the presence of this novel signal pathway may indicate that individual amino acids play specific roles for cellular proliferation and growth.

Dairy protein and leucine alter GLP-1 release and mRNA of genes involved in intestinal lipid metabolism in vitro

“…Numerous other studies have confirmed the role of leucine in activating the mTOR signaling pathway in certain cells including the intestine [37][38][39]. In the presence of leucine or other recently identified amino acids such as arginine, p70 S6 kinase and eIF-4E binding protein 1 are activated by mTOR.…”

Inhibition of the mTORC1 pathway suppresses intestinal polyp formation and reduces mortality in Apc Δ716 mice

“…These results indicate that mTORC1 pathway activation in the Apc ⌬716 intestinal polyps is independent of Erk and AMPK signaling. Nutrients such as leucine can also activate the mTORC1 pathway (21). Starved WT mice showed reduction in the S6 phosphorylation level in the normal intestinal epithelium compared with free-feeding WT mice.…”

Intrahippocampal glutamine administration inhibits mTORC1 signaling and impairs long-term memory

“…Previous studies have reported that glutamine can inhibit mTORC1 activity in vitro using cultured cells deprived of serum and amino acids, a nonphysiological condition (Nakajo et al 2005;Deldicque et al 2008). We questioned if glutamine infused into the rat hippocampus can have similar effect in vivo, as assessed by phosphorylation of the known downstream targets ribosomal S6 kinase (S6K) and ribosomal protein S6 (S6).…”

“…However, other studies have demonstrated that glutamine can either inhibit (Nakajo et al 2005;Deldicque et al 2008) or stimulate (Nicklin et al 2009;Chiu et al 2012;Willems et al 2013) mTORC1 activity, although the mechanism(s) through which this is accomplished are not yet clear. Although these and other studies that have examined the influence of glutamine on mTORC1 activity using cells cultured in vitro, they were typically carried out using serum-and/or amino acid-free conditions to induce a state of starvation.…”