L-Threonine induces heat shock protein expression and decreases apoptosis in heat-stressed intestinal epithelial cells.

Journal Article (Journal Article)

OBJECTIVES: Osmotically acting amino acids can be cytoprotective following injury. As threonine (THR) induces osmotic cell swelling, our aim was to investigate the potential for THR to induce cellular protection in intestinal epithelial cells and evaluate possible mechanisms of protection. METHODS: Cells treated with a range of THR doses were evaluated following heat stress (HS) injury. Alpha-aminoisobutyric acid (AIB), a non-metabolizable amino acid analog, was used as an osmotic control. MTS assays were used to assess cell survival. Heat shock protein (HSP) expression and cleaved caspase-3 (CC3) were evaluated via Western blot. Cell morphology and cell size were analyzed via microscopy. RESULT: Following HS, THR treatment increased cell viability in a dose dependent manner vs. non-THR treated cells (CT). The non-metabolized amino acid analogue, AIB, also increased cell survival in heat-stressed cells versus HS controls. HSP70 and HSP25 expression increased with THR and AIB treatment versus HS controls. THR also increased HSP25 in non-stressed cells. Microscopic evaluation revealed both THR and AIB preserved the structural integrity of the actin cytoskeleton in heat-stressed cells versus HS controls. THR, but not AIB, enhanced nuclear translocation of HSP25 during HS. This nuclear translocation was associated with a 60% decrease in apoptosis in heat-stressed cells with THR. No antiapoptotic effect was observed with AIB. CONCLUSIONS: This is the first demonstration that THR increases HSP70 and HSP 25 and protects cells from HS. THR's mechanism of protection may involve cytoskeletal stabilization, HSP up-regulation and nuclear translocation, and decreased apoptosis. THR's protection appears to involve both cell-swelling-dependent and -independent processes.

Full Text

Duke Authors

Cited Authors

  • Baird, CH; Niederlechner, S; Beck, R; Kallweit, AR; Wischmeyer, PE

Published Date

  • November 2013

Published In

Volume / Issue

  • 29 / 11-12

Start / End Page

  • 1404 - 1411

PubMed ID

  • 24103518

Pubmed Central ID

  • PMC4470422

Electronic International Standard Serial Number (EISSN)

  • 1873-1244

Digital Object Identifier (DOI)

  • 10.1016/j.nut.2013.05.017


  • eng

Conference Location

  • United States