ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2007
Molecular mechanisms contributing to glutamine-mediated intestinal cell survival.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 75 citations in OpenAlex.
- Protective effect and results of glutamine and partially hydrolyzed Guar gum on rats with experimental radiation enteritis.Radiation and environmental biophysics · 2026Article
- Glutamine Supplementation: A Possible Strategy to Help Mitigate Health Risks of Heat-Related Illness.Journal of nutrition and metabolism · 2024Review
- Glutaminase - A potential target for cancer treatment.BioMedicine · 2024Review
- A Novel ProbioticMicrobiology spectrum · 2022Article
- Nutritional stimulation by in-ovo feeding modulates cellular proliferation and differentiation in the small intestinal epithelium of chicks.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2022Article
- Acute heat stress-indued apoptosis in mouse skeletal muscle is not associated with alteration of glutamine homeostasis.PloS one · 2022Article
- Dietary Glutamine Inclusion Regulates Immune and Antioxidant System, as Well as Programmed Cell Death in Fish to Protect againstAntioxidants (Basel, Switzerland) · 2021Article
- Activation of Oxidative Stress Response in Cancer Generates a Druggable Dependency on Exogenous Non-essential Amino Acids.Cell metabolism · 2020Article
- Spirulina Crude Protein Promotes the Migration and Proliferation in IEC-6 Cells by Activating EGFR/MAPK Signaling Pathway.Marine drugs · 2019Article
- Metabolic traits of cancer stem cells.Disease models & mechanisms · 2018Review
- Activation of the NRF2 antioxidant program generates an imbalance in central carbon metabolism in cancer.eLife · 2017Article
- The Roles of Glutamine in the Intestine and Its Implication in Intestinal Diseases.International journal of molecular sciences · 2017Review
- Glutamine metabolism in advanced age.Nutrition reviews · 2016Review
- Glutamine and alanyl-glutamine promote crypt expansion and mTOR signaling in murine enteroids.American journal of physiology. Gastrointestinal and liver physiology · 2015Article
- Glutamine starvation enhances PCV2 replication via the phosphorylation of p38 MAPK, as promoted by reducing glutathione levels.Veterinary research · 2015Article
- Long-term intermittent glutamine supplementation repairs intestinal damage (structure and functional mass) with advanced age: assessment with plasma citrulline in a rodent model.The journal of nutrition, health & aging · 2014Article
- Expression of glutaminase is upregulated in colorectal cancer and of clinical significance.International journal of clinical and experimental pathology · 2014Article
- Therapeutic strategies impacting cancer cell glutamine metabolism.Future medicinal chemistry · 2013Review
- P38MAP kinase, but not phosphoinositol-3 kinase, signal downstream of glutamine-mediated fibronectin-integrin signaling after intestinal injury.Nutrition journal · 2013Article
- Intestinal epithelial restitution after TcdB challenge and recovery from Clostridium difficile infection in mice with alanyl-glutamine treatment.The Journal of infectious diseases · 2013Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Glutamine, the most abundant amino acid in the bloodstream, is the preferred fuel source for enterocytes and plays a vital role in the maintenance of mucosal growth. The molecular mechanisms regulating the effects of glutamine on intestinal cell growth and survival are poorly understood. Here, we show that addition of glutamine (1 mmol/l) enhanced rat intestinal epithelial (RIE)-1 cell growth; conversely, glutamine deprivation increased apoptosis as noted by increased DNA fragmentation and caspase-3 activity. To delineate signaling pathways involved in the effects of glutamine on intestinal cells, we assessed activation of extracellular signal-related kinase (ERK), protein kinase D (PKD), and phosphatidylinositol 3-kinase (PI3K)/Akt, which are important pathways in cell growth and survival. Addition of glutamine activated ERK and PKD in RIE-1 cells after a period of glutamine starvation; inhibition of ERK, but not PKD, increased cell apoptosis. Conversely, glutamine starvation alone increased phosphorylated Akt; inhibition of Akt enhanced RIE-1 cell DNA fragmentation. The role of ERK was further delineated using RIE-1 cells stably transfected with an inducible Ras. Apoptosis was significantly increased following ERK inhibition, despite Ras activation. Taken together, these results identify a critical role for the ERK signaling pathways in glutamine-mediated intestinal homeostasis. Furthermore, activation of PI3K/Akt during periods of glutamine deprivation likely occurs as a protective mechanism to limit apoptosis associated with cellular stress. Importantly, our findings provide novel mechanistic insights into the antiapoptotic effects of glutamine in the intestine.
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