Homocysteine homeostasis and betaine-homocysteine S-methyltransferase expression in the brain of hibernating bats.

Homocysteine homeostasis and betaine-homocysteine S-methyltransferase expression in the brain of hibernating bats.
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冬眠蝙蝠大脑中同型半胱氨酸稳态和甜菜碱-同型半胱氨酸S-甲基转移酶表达

DOI:
10.1371/journal.pone.0085632
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Zhang S
Zhang S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhang Y;Zhu T;Wang L;Pan YH;Zhang S

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高同型半胱氨酸是增加脑血管和神经退行性疾病发病率的重要危险因素。在哺乳动物中,补充B族维生素可以降低同型半胱氨酸水平。冬眠的哺乳动物,基本上停止摄入B族维生素,是否以及如何维持同型半胱氨酸代谢,避免脑血管影响和神经变性仍然不清楚。在这里,我们比较了迟钝蝙蝠、活跃蝙蝠和大鼠大脑中的同型半胱氨酸水平,以确定参与同型半胱氨酸稳态的分子。我们发现,尽管维生素B水平下降,但高半胱氨酸在迟钝的大脑中不会升高。在低水平的维生素B6和B12下,我们发现参与同型半胱氨酸代谢的两种主要酶(甲硫氨酸合成酶和胱硫醚β-合成酶)的总表达水平没有变化,但辅酶非依赖性甜菜碱-同型半胱氨酸S-甲基转移酶(BHMT)的表达增加了1.85倍。在基底神经节杏仁核和大脑皮质中观察到BHMT表达,其中BHMT水平在麻痹期间明显升高。这是首次报道BHMT蛋白在大脑中的表达,并表明BHMT调节冬眠蝙蝠大脑中的同型半胱氨酸。BHMT可能在冬眠哺乳动物的大脑中具有神经保护作用,对该系统的进一步研究可以扩大我们对某些脑血管和神经退行性疾病过程的生物医学理解。
Elevated homocysteine is an important risk factor that increases cerebrovascular and neurodegenerative disease morbidity. In mammals, B vitamin supplementation can reduce homocysteine levels. Whether, and how, hibernating mammals, that essentially stop ingesting B vitamins, maintain homocysteine metabolism and avoid cerebrovascular impacts and neurodegeneration remain unclear. Here, we compare homocysteine levels in the brains of torpid bats, active bats and rats to identify the molecules involved in homocysteine homeostasis. We found that homocysteine does not elevate in torpid brains, despite declining vitamin B levels. At low levels of vitamin B6 and B12, we found no change in total expression level of the two main enzymes involved in homocysteine metabolism (methionine synthase and cystathionine β-synthase), but a 1.85-fold increase in the expression of the coenzyme-independent betaine-homocysteine S-methyltransferase (BHMT). BHMT expression was observed in the amygdala of basal ganglia and the cerebral cortex where BHMT levels were clearly elevated during torpor. This is the first report of BHMT protein expression in the brain and suggests that BHMT modulates homocysteine in the brains of hibernating bats. BHMT may have a neuroprotective role in the brains of hibernating mammals and further research on this system could expand our biomedical understanding of certain cerebrovascular and neurodegenerative disease processes.
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