Abstract
We investigated the mechanisms underlying damage to rat small intestine in heat- and shake-induced stress. Eighteen Sprague-Dawley rats were randomly divided into a control group and a 3-day stressed group treated 2 h daily for 3 days on a rotary platform at 35°C and 60 r/min. Hematoxylin and eosin-stained paraffin sections of the jejunum following stress revealed shedding of the villus tip epithelial cells and lamina propria exposure. Apoptosis increased at the villus tip and extended to the basement membrane. Photomicrographs revealed that the microvilli were shorter and sparser; the nuclear envelope invaginated and gaps in the karyolemma increased; and the endoplasmic reticulum (ER) swelled significantly. Gene microarray analysis assessed 93 differentially expressed genes associated with apoptosis, ER stress, and autophagy. Relevant genes were compiled from the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Forty-one genes were involved in the regulation of apoptosis, fifteen were related to autophagy, and eleven responded to ER stress. According to KEGG, the apoptosis pathways, mitogen-activated protein kinase(MAPK) signaling pathway, the mammalian target of rapamycin (mTOR) signaling pathway, and regulation of autophagy were involved. Caspase3 (Casp3), caspase12 (Casp12), and microtubule-associate proteins 1 light chain 3(LC3) increased significantly at the villus tip while mTOR decreased; phosphorylated-AKT (P-AKT) decreased. ER stress was involved and induced autophagy and apoptosis in rat intestinal damage following heat and shake stress. Bioinformatic analysis will help determine the underlying mechanisms in stress-induced damage in the small intestine.
Highlights
Severe physical stress can cause gastrointestinal (GI) dysfunction and pathology, including stress ulcers, multiple organ dysfunction, and increased intestinal permeability [1]
We questioned how autophagy and apoptosis genes functionally interact in endoplasmic reticulum (ER) stress, and how they are regulated to achieve synergy and flexibility in response to the damage induced by diverse stresses in rat small intestine; these questions are quite complicated, and have not been well elucidated
We describe our findings from a systems biology approach to reveal potential mechanisms in heat- and shake stress-induced rat small intestine injury, especially on the third day after stress. (Our previous work showed that the rat intestine suffered most on the third day after heat and shake stress.) We report the findings of a morphological study as part of this research
Summary
Severe physical stress can cause gastrointestinal (GI) dysfunction and pathology, including stress ulcers, multiple organ dysfunction, and increased intestinal permeability [1]. Studies have reported that peripheral blood flow increases to dissipate internal body heat, resulting in a significant reduction in blood flow to the small intestine during heat stress [2] This results in intestinal mucosal barrier dysfunction and induced ischemia at the villus tip [3,4,5]. If protein aggregation is persistent and the stress cannot be resolved, signaling switches from pro-survival to pro-apoptotic [21] In this case, UPR and ER stress may play critical roles in determining cell survival or cell death, which could reveal the underlying injury mechanisms induced by heat and shake stress. We questioned how autophagy and apoptosis genes functionally interact in ER stress, and how they are regulated to achieve synergy and flexibility in response to the damage induced by diverse stresses in rat small intestine; these questions are quite complicated, and have not been well elucidated. We describe our findings from a systems biology approach to reveal potential mechanisms in heat- and shake stress-induced rat small intestine injury, especially on the third day after stress. (Our previous work showed that the rat intestine suffered most on the third day after heat and shake stress.) We report the findings of a morphological study as part of this research
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