Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0848237 (acute stress)
 4,619 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The repair of damaged gastric mucosa is a complex process involving prostaglandins (PG) and mucosal growth factors such as epidermal growth factor (EGF). Recently, we postulated that the increased occurrence of apoptosis in the gastric epithelium might be of pathophysiological importance in the development of stress lesions. The aim of the present study was to assess the effect of the pretreatment of rats, exposed to 3.5 h of water immersion and restraint stress (WRS), with EGF and PG (16,16 dmPGE(2)) on the number of stress lesions, recovery of gastric mucosa from stress and the expression of apoptosis related genes such as caspase-3 and antiapoptotic bcl-2. Rats were divided in following groups: (1) vehicle; (2) EGF 100 microg/kg i.p.; (3) 16,16 dm-PGE(2) (5 microg/kg i.g.) and caspase-1 inhibitor (ICE-I; 100 microg/kg i.p.). One hour later, the rats were exposed to 3.5 h of WRS and then sacrificed immediately (0 h) or at 6, 12, or 24 h after WRS. The number of acute gastric lesions was determined. Gastric epithelial apoptosis was assessed by TUNEL staining. In addition, mRNA expression of caspase-3, Bcl-2 and proinflammatory cytokines (IL-1 beta, TNFalpha) was assessed by RT-PCR. PGE(2) generation in gastric mucosa and luminal EGF were determined by RIA. Exposure to WRS resulted in the development of multiple acute stress erosions ( approximately 18) which almost completely healed during 24 h. The gastric blood flow was significantly reduced (approximately 70% of intact mucosa) immediately after WRS. The expression of mRNA for IL-1 beta and TNF alpha reached their peak at 12 h after stress exposure. The apoptosis rate was highest at 6 h after WRS and was accompanied by the highest caspase-3 expression. In rats pretreated with EGF or 16,16 dm-PGE(2), a significant decrease in caspase-3 mRNA and upregulation of bcl-2 mRNA as observed as compared to vehicle controls. Caspase-1 inhibitor significantly reduced the number of stress lesions. We conclude that EGF and PGE(2) accelerate healing of stress-induced lesions due to the attenuation of apoptosis via upregulation of bcl-2 in gastric mucosa. Inhibitors of apoptosis accelerate healing of stress lesions and may be potentially effective agents in the healing of damaged gastric mucosa.
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PMID:Epidermal growth factor and prostaglandin E(2) accelerate mucosal recovery from stress-induced gastric lesions via inhibition of apoptosis. 1159 61

ErbB receptor tyrosine kinases are important in maintaining the long-term structural integrity of the heart and in the induction of hypertrophy. In addition, in vivo activation of ErbB1 by epidermal growth factor (EGF) protects the heart against acute stress-induced damage. We examined here whether the ErbB sytem acutely protects the isolated heart in which stress was induced in vitro by ischemia combined with epinephrine infusion (EPI). In perfused mouse hearts, EGF induced Tyr-phosphorylation of ErbB1 but not ErbB2. Neuregulin-1beta (NRG-1beta) induced Tyr-phosphorylation of both ErbB4 and ErbB2. We also found differences in the signaling cascades activated by each growth factor. To stress the perfused mouse heart, we combined EPI with low-flow ischemia. This resulted in (i) loss of left ventricle contraction force ( + dP/dt(max)) and developed pressure (LVDP) after a short period of hypercontractility, (ii) enhanced anaerobic metabolism (lactate production), and (iii) myocyte injury (lactate dehydrogenase (LDH) release). EGF and NRG-1beta had different effects on stressed-heart contractility. EGF reduced to a half the loss of both + dP/dt(max) and LVDP. In contrast, NRG-1beta exacerbated the hypercontractility soon after reperfusion. This is coincident with a transient increase in coronary flow after reperfusion. In spite of these differences in contraction, both EGF and NRG-1beta induced similar early protection as shown by the reduction of LDH release. Our results show that the ErbB system protects the perfused heart against damage induced by acute stress. They reinforce the relevance of ErbB receptors and ligands in cardiac physiology.
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PMID:ErbB receptors protect the perfused heart against injury induced by epinephrine combined with low-flow ischemia. 1937 Apr 75