Outcome of stress on G protein-coupled receptors and hypoxia inducible factor-1α

Abstract

Stress drives neuroendocrine signals with detrimental effects to the intestinal homeostasis. The aim of this study was to evaluate the effect of stress on intestinal hypoxia response elements, including G protein-coupled receptor 41 (GPR41), GPR43, and hypoxia inducible factor (HIF)-1α. Groups of five BALB/c mice were subjected to acute (2 h per day) and chronic (2 h per day for 4 days) stress induced by restraint, and the results were compared to those of an unstressed control group. Whole mucosal samples from the colon were collected to evaluate the expression of GPR41, GPR43 and HIF-1α using Western blot chemiluminescent analysis. Compared to the control group, in the chronic stress group the expression of GPR43 (P = 0.0092) and HIF-1α (P < 0.0001) were significantly lower and the expression of GPR41 was similar (P = 0.9184); acute stress significantly increased HIF-1α expression (P = 0.0030) and increased GPR41 expression (P = 0.0937), without affecting GPR43 (P = 0.9184). These findings offer insights into the modulation of hypoxia response elements under stress conditions and their pharmacological implications for developing drugs that mitigate the effects of stress on intestinal homeostasis.

Keywords: GPR41/GPR43; HIF-1α; colon; hypoxia; restraint stress.

Figure 1

Representative Western blots of GPR41 and GPR43 in colonic mucosal samples of mice in the control (left), acute stress (middle) and chronic stress (right) groups. CT, control; AS, acute stress; CS, chronic stress. The results of densitometry analysis are expressed in arbitrary units (AU, y-axis) for each group (x-axis). The expression of the housekeeping protein β-actin is expressed as mean ± s.d., in AU (n = 5 mice per group).

Figure 2

Representative Western blots of HIF-αβ in colonic whole mucosal samples of control (left), acute stress (middle) and chronic stress (right) groups. The results of densitometry analysis are expressed in arbitrary units (AU, y-axis) for each group (x-axis). The expression of the housekeeping protein β-actin is expressed as mean ± s.d., in AU (n = 5 mice per group).