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)

To test the hypothesis that the aging mammalian heart and brain might have increased vulnerability to acute stress, DNA fragmentation was studied after hypoxia-reoygenation in young adult (6 months) and old (22-24 months) F344 rats. Heart and brain tissue were examined at the following time points: 30, 60, or 90 min of hypoxia (H, 5% O2, 95% N2) plus 2 h of reoxygenation (R, room air, 21% O2). With increasing duration of hypoxia preceding the reoxygenation, the extent of DNA fragmentation (in situ terminal dUTP nick end labeling, TUNEL, positive cells) was progressively higher in both age groups, greater in the old compared to that of the young adult rat. The levels of the anti-apoptotic proteins bcl-2 and bcl-xL, were similar in young and old at baseline and tended to increase in both age groups after hypoxia/reoxygenation. The pro-apoptotic protein, bax, was higher at baseline in the old; it rose after hypoxia/reoxygenation in the young adult heart and brain, but was unchanged in the old heart and was decreased in the old brain. The ratios of bcl-2/bax and of bcl-xL/bax were higher in the old heart and brain compared to that in the young adult after hypoxia/reoxygenation. Thus, compared to that of the young adult, the heart and brain of the old rat have lower thresholds and are more vulnerable to injury induced by hypoxia/reoxygenation, despite rapid and heightened expression of the anti-apoptotic proteins bcl-2 and bcl-xl. This could be due partly to the age-associated increase in the basal expression of the pro-apoptotic protein bax, as well as possibly other factors.
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PMID:Influence of age on hypoxia/reoxygenation-induced DNA fragmentation and bcl-2, bcl-xl, bax and fas in the rat heart and brain. 1065 80

Successful adaptation to stress involves actions of glucocorticoid receptor (GR), a steroid-dependent transcription factor, abundant in hippocampus. Another transcription factor, nuclear factor kappa B (NFjB) is considered as an important stress sensor implicated in adaptive synaptic plasticity. Numerous stress-related genes are regulated by both hippocampal GR and NFjB, including neural cell adhesion molecules (NCAM and L1), involved in plasticity, and genes that encode apoptotic proteins (bax and bcl-2). We presumed that the ratio of nuclear NFjB to nuclear GR may determine the degree of proplastic or proapoptotic signaling under stress. To test this presumption we have investigated effects of acute, chronic and combined stress on compartmental levels and ratios of NFjB and GR proteins, and in parallel, changes in their mRNA expression. In addition, the expression of plasticity (NCAM, L1) and apoptotic (bax, bcl-2) genes, as well as, Bax and Bcl-2 proteins redistribution between mitochondrial and cytoplasmic compartments, were followed. When glucocorticoid levels were low, as found in chronic stress, GR was not efficiently translocated to the nucleus. This resulted in its lower nuclear level relative to the nuclear NFjB. Such conditions did not affect proplastic induction of NCAM mRNA, but were related to the onset of proapoptotic signaling illustrated by relocation of mitochondrial Bcl-2 protein to its soluble cytoplasmic form. Because these Bcl-2 rearrangements were not reversed by subsequent acute stress, representing more stable alterations, it is concluded that chronic social isolation of Wistar rats led to the initiation of proapoptotic signaling that may be etiologically related to compromised adaptive response of central nervous system.
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PMID:Chronic social isolation is related to both upregulation of plasticity genes and initiation of proapoptotic signaling in Wistar rat hippocampus. 1966 92