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981.
Toxicity of Dopamine to Striatal Neurons In Vitro and Potentiation of Cell Death by a Mitochondrial Inhibitor 总被引:8,自引:2,他引:6
B. A. McLaughlin †D. Nelson †‡M. Ereciska † M.-F. Chesselet 《Journal of neurochemistry》1998,70(6):2406-2415
Abstract: Intrastriatal injections of the mitochondrial toxins malonate and 3-nitropropionic acid produce selective cell death similar to that seen in transient ischemia and Huntington's disease. The extent of cell death can be attenuated by pharmacological or surgical blockade of cortical glutamatergic input. It is not known, however, if dopamine contributes to toxicity caused by inhibition of mitochondrial function. Exposure of primary striatal cultures to dopamine resulted in dose-dependent death of neurons. Addition of medium supplement containing free radical scavengers and antioxidants decreased neuronal loss. At high concentrations of the amine, cell death was predominantly apoptotic. Methyl malonate was used to inhibit activity of the mitochondrial respiratory chain. Neither methyl malonate (50 µ M ) nor dopamine (2.5 µ M ) caused significant toxicity when added individually to cultures, whereas simultaneous addition of both compounds killed 60% of neurons. Addition of antioxidants and free radical scavengers to the incubation medium prevented this cell death. Dopamine (up to 250 µ M ) did not alter the ATP/ADP ratio after a 6-h incubation. Methyl malonate, at 500 µ M , reduced the ATP/ADP ratio by ∼30% after 6 h; this decrease was not augmented by coincubation with 25 µ M dopamine. Our results suggest that dopamine causes primarily apoptotic death of striatal neurons in culture without damaging cells by an early adverse action on oxidative phosphorylation. However, when combined with minimal inhibition of mitochondrial function, dopamine neurotoxicity is markedly enhanced. 相似文献
982.
The results of recent randomized trials to test the influence of antioxidants on coronary-event rates and prognosis in patients
with coronary-artery disease were disappointing. In none of these studies did the use of vitamin E improve prognosis. In contrast,
treatment of coronary-artery disease with angiotensin-converting-enzyme (ACE) inhibitors reduced coronary-event rates and
improved prognosis. ACE inhibition prevents the formation of angiotensin II, which has been shown to be a potent stimulus
of superoxide-producing enzymes in atherosclerosis. The findings suggest that inhibition of superoxide production at enzymatic
levels, rather than symptomatic superoxide scavenging, may be the better choice of treatment. 相似文献
983.
984.
985.
In 72 newborn children (37 boys and 35 girls) who suffered from prenatal hypoxia and were born in an asphyxic state, we measured
the level of melatonin in the umbilicial blood and observed clinical manifestations of the adaptation/stress syndrome. These
data were compared with the results of morphological examination of the epiphyses from 27 stillborns (15 boys and 12 girls)
who perished because of heavy prenatal hypoxia. The level of melatonin in the blood of ill newborn girls was much higher than
that in boys, and both these indices were about two times higher than those in respective groups of healthy newborn children.
At the same time, the pathomorphological examination showed that active epiphyseal cell units in the male fetuses were much
more numerous. The results show that the epiphysis plays a significant role in determination of the sex-related dimorphism
of the adaptation/stress syndrome in newborn children suffering from hypoxia- and asphyxia-evoked heavy CNS damage. The reasons
and consequences of more intensive morphofunctional loading of the epiphyseal system in the male fetuses are discussed. 相似文献
986.
987.
988.
The purpose of this review is to provide a global perspective on Oncorhynchus salmonine introductions and put-and-take fisheries based on modern stocking programs, with special emphasis on freshwater
ecosystems. We survey the global introductions of nine selected salmonines of the genus Oncorhynchus: golden trout, cutthroat trout, pink salmon, chum salmon, coho salmon, masu/cherry salmon, rainbow trout/steelhead, sockeye
salmon/kokanee, and chinook salmon. The information is organized on a geographical basis by continent, and then by species
and chronology. Two different objectives and associated definitions of ‘success’ for introductions are distinguished: (a)
seed introduction: release of individuals with the purpose of creating a wild-reproducing, self-sustaining population; and
(b) put-and-take introduction: release of individuals with the purpose of maintaining some level of wild population abundance,
regardless of wild reproduction. We identify four major phenomena regarding global salmonine introductions: (1) general inadequacy
of documentation regarding introductions; (2) a fundamental disconnect between management actions and ecological consequences
of introductions; (3) the importance of global climate change on success of previous and future introductions; and (4) the
significance of aquaculture as a key uncertainty in accidental introductions. We conclude this review with a recognition of
the need to terminate ongoing stocking programs for introduced salmonines worldwide. 相似文献
989.
990.
A new aspartic proteinase was isolated from porcine intestine mucosa by affinity chromatography on pepstatin-Sepharose 4B and gel filtration on Sephadex G-100. The enzyme was purified 1600-fold and appeared homogeneous upon polyacrylamide gel electrophoresis. The proteinase has a Mr 60 000 +/- 4000 Da. During sodium dodecyl sulfate polyacrylamide gel electrophoresis the enzyme produced a single protein band (Mr 30 000 +/- 3000 Da). Isoelectric focusing revealed that the enzyme has several multiple forms (pI 6.9, 7.5, 8,0). The enzyme is a glycoprotein containing 5.9% of carbohydrates; the mannose to galactose ratio is 1:3. The amino acid composition of the enzyme was studied. The proteinase splits an oxidized insulin B-chain and synthetic substrates. The pH optimum is 3.2. The enzyme is immunologically identical to porcine spleen cathepsin D. 相似文献