Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transglutaminase (TG, EC 2.3.2.13) activity and levels of putrescine (a natural acyl-acceptor in the transglutaminase reaction) were measured in rat brains after 30 min ischemia and 8 or 24 h recirculation. TG activity was significantly increased in the striatum and hippocampus already during cerebral ischemia and, more pronounced, after 8 and 24 h recirculation. In the cortex, in contrast, TG activity did not change during ischemia and 8 h recirculation but was significantly increased after 24 h recirculation. Putrescine levels were sharply increased after 8 h recirculation and even further after 24 h recirculation. It is suggested that in vivo during ischemia and early recirculation, when cells are overloaded with calcium ions, a pathological increase in the TG-catalyzed cross-linking of proteins may be apparent especially in the nerve endings of the hippocampus where the intrinsic concentration of the acyl-donor (protein-bound glutamyl-moiety) has been shown to be high.
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PMID:Transglutaminase activity in reversible cerebral ischemia in the rat. 197 Jan 43

Brain injury of the ischemia/reperfusion type induces neuronal damage, mainly by excitatory amino acid release, intracellular Ca(2+) overload and reactive oxygen species production. We have previously demonstrated that glutamate exposure increased transglutaminase activity and transglutaminase 2 expression in cultured cerebellar granule cells and astrocytes. The aim of this study is to evaluate changes in transglutaminase activity and expression using a gerbil model of global cerebral ischemia. Moreover, the distribution and amounts of different transglutaminase isoforms were examined. Transglutaminase activity was measured by incorporation of [(3)H]putrescine into dimethylcasein throughout 48 h of reperfusion following a 3 min occlusion. Compared to sham-operated brains, significant increases were found in the ischemic hippocampus at 24 h of reperfusion, while minor changes were observed in the cortex. RT-PCR demonstrated the presence of significant mRNA amounts of transglutaminase 2 and transglutaminase 1, both in the hippocampus and the cerebral cortex, while low levels were found for transglutaminase 3 transcripts. Interestingly, transglutaminase 2 and transglutaminase 1 mRNAs were 4-fold and 2-fold increased, respectively, in the ischemic hippocampus after 24 h of reperfusion. Western blot analysis of transglutaminase 2 expression confirmed a strong up-regulation in the ischemic hippocampus. However, it is possible to hypothesize that different expression rates of transglutaminase isoforms may be dependent on different responsiveness of their transcription regulatory elements to intracellular calcium overload following excitotoxic cell injury. Our results suggest that increases in transglutaminases may be part of the tissue stress response in global brain ischemia.
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PMID:Transglutaminase activity and transglutaminase mRNA transcripts in gerbil brain ischemia. 1517 9

Neurodegeneration induced by excitotoxicity is a common feature in various neurological disorders. This pathological condition is caused by prolonged stimulation of glutamate receptor subtypes, followed by both intracellular Ca2+ overload and activation of specific genes, resulting in synthesis of enzymes involved in cell stress response. Using experimental in vitro models of excitotoxicity, we demonstrated that glutamate exposure up-regulated tissue transglutaminase in primary cultures of both cerebellar granule cells and astrocytes. These changes were consequent to receptor-mediated Ca2+ influx, as demonstrated by the inhibition with selective antagonists, MK-801 and GYKI 52466. Early increases in different transglutaminase isoforms were also observed in global cerebral ischemia, which closely resembles neuronal damage caused by NMDA receptor activation. These findings agree with a postulated role for transglutaminases in molecular mechanisms of several neurodegenerative diseases. Indeed, increased cross-linking reactions could be of pathologic relevance, as part of biochemical changes observed in neurological disorders.
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PMID:Excitotoxic and post-ischemic neurodegeneration: Involvement of transglutaminases. 1536 7

Vasospasm is known to contribute to delayed cerebral ischemia following subarachnoid hemorrhage (SAH). We hypothesized that vasospasm initiates structural changes within the vessel wall, possibly aggravating ischemia and leading to resistance to vasodilator treatment. We therefore investigated the effect of blood on cerebral arteries with respect to contractile activation and vascular remodeling. In vitro experiments on rodent basilar and middle cerebral arteries showed a gradual contraction in response to overnight exposure to blood. After incubation with blood, a clear inward remodeling was found, reducing the caliber of the passive vessel. The transglutaminase inhibitor L682.777 fully prevented this remodeling. Translation of the in vitro findings to an in vivo SAH model was attempted in rats, using both a single prechiasmatic blood injection model and a double cisterna magna injection model, and in mice, using a single prechiasmatic blood injection. However, we found no substantial changes in active or passive biomechanical properties in vivo. We conclude that extravascular blood can induce matrix remodeling in cerebral arteries, which reduces vascular caliber. This remodeling depends on transglutaminase activity. However, the current rodent SAH models do not permit in vivo confirmation of this mechanism.
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PMID:Cerebral Artery Remodeling in Rodent Models of Subarachnoid Hemorrhage. 2618 61