High sodium chloride intake decreases betaine-homocysteine S-methyltransferase expression in guinea pig liver and kidney

High sodium chloride intake decreases betaine-homocysteine S-methyltransferase expression in guinea pig liver and kidney
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DOI:
10.1152/ajpregu.00406.2004
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发表时间:
2005-01-01
影响因子:
2.8
通讯作者:
Garrow, TA
Garrow, TA
中科院分区:
医学3区
文献类型:
--
作者:
Delgado-Reyes, CV;Garrow, TA

文献摘要

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甜菜碱-同型半胱氨酸S-甲基转移酶(BHMT)是已知的唯一分解代谢甜菜碱的酶。除了作为BHMT的底物外,甜菜碱还用作在高细胞外渗透压条件下在肾髓质中积累的维生素D保护剂。调节甜菜碱在作为甲基供体的使用和作为渗透保护剂的积累之间分配的机制尚未完全了解。本研究的目的是确定BHMT表达是否受盐摄入量的调节。该报告显示,豚鼠在肝脏、肾脏和胰腺中表达BHMT,与提供未经处理的自来水的动物相比,饮用含高水平盐的自来水的豚鼠肾脏和肝脏中BHMT mRNA的稳态水平降低了68%和93%。食用盐水的动物肝脏和肾脏中的BHMT活性也降低了50%,两个器官中的稳态蛋白水平也降低了30%。胰腺BHMT活性和蛋白水平不受高盐处理的影响。饮用盐水的豚鼠肝脏和肾脏BHMT表达下调的复杂机制仍有待阐明,但这种下调的生理意义可能是在高细胞外渗透压条件下加速甜菜碱向肾髓质的转运和积累。
Betaine-homocysteine S-methyltransferase (BHMT) is the only enzyme known to catabolize betaine. In addition to being a substrate for BHMT, betaine also functions as an osmoprotectant that accumulates in the kidney medulla under conditions of high extracellular osmolarity. The mechanisms that regulate the partitioning of betaine between its use as a methyl donor and its accumulation as an osmoprotectant are not completely understood. The aim of this study was to determine whether BHMT expression is regulated by salt intake. This report shows that guinea pigs express BHMT in the liver, kidney, and pancreas and that the steady-state levels of BHMT mRNA in kidney and liver decrease 68% and 93% in guinea pigs consuming tap water containing high levels of salt compared with animals provided untreated tap water. The animals consuming the salt water also had similar to50% less BHMT activity in the liver and kidney, and steady-state protein levels decreased similar to30% in both organs. Pancreatic BHMT activity and protein levels were unaffected by the high salt treatment. The complex mechanisms involved in the downregulation of hepatic and renal BHMT expression in guinea pigs drinking salt water remain to be clarified, but the physiological significance of this downregulation may be to expedite the transport and accumulation of betaine into the kidney medulla under conditions of high extracellular osmolarity.