Levesque P C, Atchison W D
Department of Pharmacology and Toxicology, Michigan State University, East Lansing.
J Pharmacol Exp Ther. 1991 Jan;256(1):236-42.
In vitro effects of methylmercury (MeHg) on Ca2+ transport and respiratory control of mitochondria isolated from rat forebrain were examined to determine whether MeHg disrupted sequestration of Ca2+ by neuronal mitochondria. Uptake of 45Ca2+ by mitochondria and release of 45Ca2+ from preloaded mitochondria were measured in the presence and absence of ATP. Release of 45Ca2+ from preloaded mitochondria by MeHg was measured in the presence and absence of ruthenium red (RR), a putative inhibitor of the mitochondrial Ca2+ uptake uniporter. During incubation intervals ranging from 10 sec to 5 min, 10 microM MeHg reduced mitochondrial uptake of 45Ca2+ by about 50% and 100 microM MeHg completely prevented 45Ca2+ uptake. These effects of MeHg occurred in both the presence and absence of ATP. Exposure of mitochondria preloaded with 45Ca2+ to either 10 microM or 100 microM MeHg for 10 sec resulted in increased efflux of 45Ca2+ of 10% and 65%, respectively, in both the absence and presence of ATP. Loading mitochondria with 45Ca2+ in the presence of 20 microM RR reduced total uptake of 45Ca2+ and greatly attenuated MeHg-induced release of 45Ca2+ from mitochondria. RR did not inhibit the effects of MeHg on Ca2+ release by merely preventing the binding of MeHg to mitochondria because RR did not alter mitochondrial binding of methyl[203Hg]. The ratio of state 3 to state 4 respiration (respiratory control ratio) was measured as a means of assessing functional integrity of isolated mitochondria in the absence and presence of MeHg. Control ratios of from 3 to 5 were only marginally reduced by 2 microM MeHg but were greatly reduced by 10 and 20 microM MeHg.(ABSTRACT TRUNCATED AT 250 WORDS)
研究了甲基汞（MeHg）对从大鼠前脑分离的线粒体钙转运和呼吸控制的体外影响，以确定MeHg是否破坏神经元线粒体对钙的隔离。在有和没有ATP的情况下，测量线粒体对45Ca2+的摄取以及预加载线粒体中45Ca2+的释放。在有和没有钌红（RR）（一种推测的线粒体钙摄取单向转运体抑制剂）的情况下，测量MeHg诱导预加载线粒体释放45Ca2+的情况。在10秒至5分钟的孵育间隔期间，10微摩尔MeHg使线粒体对45Ca2+的摄取减少约50%，100微摩尔MeHg完全阻止45Ca2+的摄取。MeHg的这些作用在有和没有ATP的情况下均会发生。将预加载45Ca2+的线粒体暴露于10微摩尔或100微摩尔MeHg中10秒，在没有和有ATP的情况下，45Ca2+的流出分别增加了10%和65%。在20微摩尔RR存在的情况下用45Ca2+加载线粒体，会降低45Ca2+的总摄取量，并大大减弱MeHg诱导的线粒体释放45Ca2+。RR并没有仅仅通过阻止MeHg与线粒体的结合来抑制MeHg对钙释放的影响，因为RR并没有改变甲基[203Hg]与线粒体的结合。测量状态3与状态4呼吸的比率（呼吸控制率），作为评估在有和没有MeHg的情况下分离线粒体功能完整性的一种方法。2微摩尔MeHg仅使3至5的对照比率略有降低，但10和20微摩尔MeHg使其大大降低。（摘要截短于250字）
