Non-invasive monitoring of L-2-oxothiazolidine-4-carboxylate metabolism in the rat brain by in vivo 13C magnetic resonance spectroscopy.
Non-invasive monitoring of L-2-oxothiazolidine-4-carboxylate metabolism in the rat brain by in vivo 13C magnetic resonance spectroscopy.
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DOI：
10.1007/s11064-010-0362-5
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发表时间：
2011-03
影响因子：
4.4
通讯作者：
Thelwall, Peter E.
中科院分区：
文献类型：
--
作者：
Gamcsik, Michael;Clark, M. Daniel;Ludeman, Susan M.;Springer, James B.;D'Alessandro, Michael A.;Simpson, Nicholas E.;Pourdeyhimi, Roxana;Johnson, C. Bryce;Teeter, Stephanie D.;Blackband, Stephen J.;Thelwall, Peter E.
半胱氨酸前体L-2-氧代噻唑烷-4-羧酸盐（OTZ，原半胱氨酸）可以提高某些组织中的半胱氨酸浓度，从而提高谷胱甘肽水平。因此，OTZ已被提议作为对抗氧化应激的前药。我们合成了稳定同位素标记的OTZ（即L-2-oxo-[5- 13 C]-thiazolidine-4-carboxylic acid，13 C-OTZ），并利用13 C磁共振波谱技术跟踪了其在大鼠脑内的体内摄取和代谢。尽管通过体内光谱法在推注剂量后在大鼠脑中可检测到13 C-OTZ的摄取和清除，但未检测到同位素标记掺入脑谷胱甘肽中。然而，连续输注13 C-OTZ超过20小时，导致13 C-标记掺入谷胱甘肽，牛磺酸，亚牛磺酸和乳酸的水平足以通过体内磁共振光谱检测。通过质谱法对脑组织提取物进行检查，证实在用团注剂量治疗的大鼠中仅低水平的同位素掺入谷胱甘肽中，并且在连续输注20小时后水平高得多。与以前的一些研究相反，OTZ的推注给药并没有改变脑谷胱甘肽水平。即使连续输注OTZ超过20小时也未能提高脑谷胱甘肽水平。这些研究表明，在体内磁共振无创监测抗氧化剂的吸收和代谢在完整的大脑的效用。这些类型的实验可用于评估各种干预措施对维持大脑谷胱甘肽的功效。
The cysteine precursor L-2-oxothiazolidine-4-carboxylate (OTZ, procysteine) can raise cysteine concentration, and thus glutathione levels, in some tissues. OTZ has therefore been proposed as a prodrug for combating oxidative stress. We have synthesized stable isotope labeled OTZ (i.e. L-2-oxo-[5-13C]-thiazolidine-4-carboxylate, 13C-OTZ) and tracked its uptake and metabolism in vivo in rat brain by 13C magnetic resonance spectroscopy. Although uptake and clearance of 13C-OTZ was detectable in rat brain following a bolus dose by in vivo spectroscopy, no incorporation of isotope label into brain glutathione was detectable. Continuous infusion of 13C-OTZ over 20 h, however, resulted in 13C-label incorporation into glutathione, taurine, hypotaurine and lactate at levels sufficient for detection by in vivo magnetic resonance spectroscopy. Examination of brain tissue extracts by mass spectrometry confirmed only low levels of isotope incorporation into glutathione in rats treated with a bolus dose and much higher levels after 20 h of continuous infusion. In contrast to some previous studies, bolus administration of OTZ did not alter brain glutathione levels. Even a continuous infusion of OTZ over 20 h failed to raise brain glutathione levels. These studies demonstrate the utility of in vivo magnetic resonance for non-invasive monitoring of antioxidant uptake and metabolism in intact brain. These types of experiments can be used to evaluate the efficacy of various interventions for maintenance of brain glutathione.
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DOI：
10.1056/nejmct0708278
发表时间：
2008-07-17
期刊：
The New England journal of medicine
影响因子：
--
作者：
Heard KJ
通讯作者：
Heard KJ
DOI：
10.1152/ajpendo.00053.2007
发表时间：
2007-07-01
影响因子：
5.1
作者：
Dominy, John E., Jr.;Hwang, Jesse;Stipanuk, Martha H.
通讯作者：
Stipanuk, Martha H.
影响因子：
1.6
作者：
Arfsten, Darryl P.;Johnson, Eric W.;Bobb, Andrew J.
通讯作者：
Bobb, Andrew J.
影响因子：
3
作者：
Millis, KK;Lesko, SA;Gamcsik, MP
通讯作者：
Gamcsik, MP
影响因子：
4.4
作者：
PASANTESMORALES, H;CHATAGNER, F;MANDEL, P
通讯作者：
MANDEL, P