Effect of calcium antagonists on postischemic protein biosynthesis in gerbil brain.

Xie, Yaxia; Seo, Kuniko; Ishimaru, Katsuyuki; Hossmann, Konstantin‐Alexander

doi:10.1161/01.str.23.1.87

Cited by 10 publications

(4 citation statements)

References 32 publications

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“…This latter finding supports the hypothesis that calcium antagonists have a protective effect on acid-base homeostasis (Bielenberg et al 1990). Administration of nimodipine after experimental ischaemia had no effect on protein biosynthesis in gerbil brain (Xie et al 1992).…”

Section: Metabolic Effectsmentioning

confidence: 82%

Nimodipine

Wadworth¹,

McTavish²

1992

Drugs & Aging

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Nimodipine is a dihydropyridine calcium antagonist which dilates cerebral blood vessels and increases cerebral blood flow in animals and humans. Preliminary findings reveal its potential benefit for the treatment of a wide range of cerebrovascular disorders, particularly for prophylaxis and treatment of delayed ischaemic neurological deficits resulting from cerebral vasospasm in patients with subarachnoid haemorrhage. Studies involving patients aged up to 79 years have confirmed these preliminary findings by showing that nimodipine reduces the incidence of severe ischaemic deficit after subarachnoid haemorrhage. Initial results from studies of patients with acute ischaemic stroke indicate that nimodipine, started within 72 hours of onset, improved recovery, particularly in patients over 65 years. However, other investigators have found no marked difference in 6-month mortality or morbidity rates of stroke patients aged up to 97 years. Findings from other studies suggest that nimodipine may improve symptoms of cognitive dysfunction in elderly patients. Nimodipine is well tolerated by both younger and older patients. The most frequently reported adverse event has been hypotension. Thus, nimodipine therapy offers important benefits as part of the approach to management of patients with subarachnoid haemorrhage and has potential in other cerebral disorders, including stroke and impaired cognitive function, although confirmation of initial results in patients with cerebral impairment are required.

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Section: Metabolic Effectsmentioning

confidence: 82%

Nimodipine

Wadworth¹,

McTavish²

1992

Drugs & Aging

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“…Prolonged inhibition of protein synthesis, if uncompensated by a decrease in breakdown of protein, would clearly lead to massive changes in cell properties and cell death. Protein synthesis is a complex process that is critically dependent on energy charge (936), intracellular K ϩ /Na ϩ (672), and the integrity and phosphorylation level of a large number of proteins and RNA species (1230). It is strongly and permanently inhibited by ischemia in vulnerable cells, and the question is whether or not this is responsible for any forms of ischemic cell death.…”

Section: Global Inhibition Of Protein Synthesismentioning

confidence: 99%

“…There is conflict as to the basis for this inhibition. A priori, phosphorylation of EIF-2a or dephosphorylation of guanine nucleotide exchange factor (GEF) are the most likely inhibitory points (466,1230). One set of studies concluded that there was no increase in EIF-2a phosphorylation but demonstrated a decrease in GEF activity that appeared to be due to dephosphorylation of a site that was normally phosphorylated by a tyrosine kinase.…”

Section: Basis For Prolonged Inhibition Of Protein Synthesismentioning

confidence: 99%

Ischemic Cell Death in Brain Neurons

Lipton

1999

Physiological Reviews

2,722

2,085

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This review is directed at understanding how neuronal death occurs in two distinct insults, global ischemia and focal ischemia. These are the two principal rodent models for human disease. Cell death occurs by a necrotic pathway characterized by either ischemic/homogenizing cell change or edematous cell change. Death also occurs via an apoptotic-like pathway that is characterized, minimally, by DNA laddering and a dependence on caspase activity and, optimally, by those properties, additional characteristic protein and phospholipid changes, and morphological attributes of apoptosis. Death may also occur by autophagocytosis. The cell death process has four major stages. The first, the induction stage, includes several changes initiated by ischemia and reperfusion that are very likely to play major roles in cell death. These include inhibition (and subsequent reactivation) of electron transport, decreased ATP, decreased pH, increased cell Ca(2+), release of glutamate, increased arachidonic acid, and also gene activation leading to cytokine synthesis, synthesis of enzymes involved in free radical production, and accumulation of leukocytes. These changes lead to the activation of five damaging events, termed perpetrators. These are the damaging actions of free radicals and their product peroxynitrite, the actions of the Ca(2+)-dependent protease calpain, the activity of phospholipases, the activity of poly-ADPribose polymerase (PARP), and the activation of the apoptotic pathway. The second stage of cell death involves the long-term changes in macromolecules or key metabolites that are caused by the perpetrators. The third stage of cell death involves long-term damaging effects of these macromolecular and metabolite changes, and of some of the induction processes, on critical cell functions and structures that lead to the defined end stages of cell damage. These targeted functions and structures include the plasmalemma, the mitochondria, the cytoskeleton, protein synthesis, and kinase activities. The fourth stage is the progression to the morphological and biochemical end stages of cell death. Of these four stages, the last two are the least well understood. Quite little is known of how the perpetrators affect the structures and functions and whether and how each of these changes contribute to cell death. According to this description, the key step in ischemic cell death is adequate activation of the perpetrators, and thus a major unifying thread of the review is a consideration of how the changes occurring during and after ischemia, including gene activation and synthesis of new proteins, conspire to produce damaging levels of free radicals and peroxynitrite, to activate calpain and other Ca(2+)-driven processes that are damaging, and to initiate the apoptotic process. Although it is not fully established for all cases, the major driving force for the necrotic cell death process, and very possibly the other processes, appears to be the generation of free radicals and peroxynitrite. Effects of a large number of damagin...

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“…The rate of L-[methyl-'H]-methionine incorporation into protein was measured using a modification of the method described by Xie et al 21 Tissue samples were weighed and homogenized with a polytron in 2 mL ice-cold water. After removing an aliquot to determine total tritium levels, 2.5 mL of ice-cold 10% trichloroacetic acid (TCA) was added and incubated on ice for 30 minutes.…”

mentioning

confidence: 99%

Evidence supporting a role for programmed cell death in focal cerebral ischemia in rats.

Linnik¹,

Zobrist²,

Hatfield³

1993

Stroke

663

292

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Background and Purpose: Cells die by one of two mechanisms, necrosis or programmed cell death. Necrosis has been implicated in stroke and occurs when the cytoplasmic membrane is compromised. Programmed cell death requires protein synthesis and often involves endonucleolytic cleavage of the cellular DNA. We assessed the potential contribution of programmed cell death to ischemia-induced neuronal death.

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Effect of calcium antagonists on postischemic protein biosynthesis in gerbil brain.

Cited by 10 publications

References 32 publications

Nimodipine

Nimodipine

Ischemic Cell Death in Brain Neurons

Evidence supporting a role for programmed cell death in focal cerebral ischemia in rats.

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