Abstract
Stress-induced glucocorticoid elevation is a highly conserved response among vertebrates. This facilitates stress adaptation and the mode of action involves activation of the intracellular glucocorticoid receptor leading to the modulation of target gene expression. However, this genomic effect is slow acting and, therefore, a role for glucocorticoid in the rapid response to stress is unclear. Here we show that stress levels of cortisol, the primary glucocorticoid in teleosts, rapidly fluidizes rainbow trout (Oncorhynchus mykiss) liver plasma membranes in vitro. This involved incorporation of the steroid into the lipid domains, as cortisol coupled to a membrane impermeable peptide moiety, did not affect membrane order. Studies confirmed that cortisol, but not sex steroids, increases liver plasma membrane fluidity. Atomic force microscopy revealed cortisol-mediated changes to membrane surface topography and viscoelasticity confirming changes to membrane order. Treating trout hepatocytes with stress levels of cortisol led to the modulation of cell signaling pathways, including the phosphorylation status of putative PKA, PKC and AKT substrate proteins within 10 minutes. The phosphorylation by protein kinases in the presence of cortisol was consistent with that seen with benzyl alcohol, a known membrane fluidizer. Our results suggest that biophysical changes to plasma membrane properties, triggered by stressor-induced glucocorticoid elevation, act as a nonspecific stress response and may rapidly modulate acute stress-signaling pathways.
Highlights
The neuroendocrine response to stress is highly conserved among vertebrates and essential to reestablish homeostasis [1]
When cortisol was coupled to a peptide moiety (PEP) to make it membrane impermeable, there was no significant effect on membrane fluidity (Fig. 1C)
Hepatocyte Response To investigate whether physiochemical changes in the plasma membrane are capable of stimulating intracellular signaling in trout hepatocytes we examined the phosphorylation of protein kinase A (PKA), protein kinase C (PKC) and AKT-substrate proteins in response to benzyl alcohol, a known membrane fluidizer, and cortisol
Summary
The neuroendocrine response to stress is highly conserved among vertebrates and essential to reestablish homeostasis [1]. The principal stress hormones, epinephrine and glucocorticoid, have critical functions in the stress adaptation process [2]. The fight-or-flight response involves the activation of the sympathetic nervous system leading to the rapid release of epinephrine from chromaffin cells [2]. Glucocorticoid hormone release occurs in response to activation of the hypothalamus-pituitary-adrenal (HPA) axis [2], and reaches peak levels only after the catecholamine response [1]. In addition to the slower genomic actions, glucocorticoid elicits rapid effects that are independent of gene transcription and are broadly categorized as nongenomic signaling [3], but a role for this in stress adaptation is unclear [4]
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