Lynch Sean M
Department of Biochemistry, Midwestern University, Downers Grove, IL 60515, USA.
Nutr Res. 2008 Sep;28(9):615-9. doi: 10.1016/j.nutres.2008.05.010.
Oxidation of human low-density lipoprotein (LDL) is centrally involved in the development of cardiovascular diseases. This study investigated whether homocysteine-mediated thiolation of LDL rendered it more susceptible to oxidation by iron. After in vitro exposure to homocysteine thiolactone for 60 minutes, LDL's thiol content increased from 26 +/- 5 (control) to 224 +/- 20 nmol/mg of protein (thiolated; P < .0001). Control and thiolated LDL (0.2 mg of protein per milliliter) were incubated with either redox active iron (Fe(3+); 10 micromol/L) or, as a positive control, copper (Cu(2+); 10 micromol/L). Consistent with the observation of others, thiolation decreased Cu(2+)-dependent formation of lipid oxidation products in LDL (17 +/- 16 nmol/mg of protein formed in thiolated LDL, compared with 81 +/- 21 nmol/mg of protein in control, during 6 hours of incubation; P < .01). Thiolation had no effect, however, on Fe(3+)-mediated oxidation of LDL with lipid oxidation products remaining essentially nondetectable during prolonged incubation (up to 48 hours). Thiolation similarly had no effect on oxidation of LDL (0.2 mg of protein per milliliter) by heme-complexed iron (hemin; 10 micromol/L), with lipid oxidation products increasing to 24 +/- 1 and 27 +/- 4 nmol/mg of protein for control and thiolated LDL, respectively, during 6 hours of incubation (P > .05). Similar results were observed using LDL with varying degrees of thiolation (29 +/- 5, 85 +/- 14, 130 +/- 15, and 213 +/- 19 nmol of thiol per milligram of protein). In conclusion, these results demonstrate that thiolation has no effect on LDL's susceptibility to iron-mediated oxidation.
人低密度脂蛋白（LDL）的氧化在心血管疾病的发展过程中起着核心作用。本研究调查了同型半胱氨酸介导的LDL硫醇化是否使其更易被铁氧化。在体外暴露于同型半胱氨酸硫内酯60分钟后，LDL的硫醇含量从26±5（对照）增加至224±20 nmol/mg蛋白质（硫醇化；P <.0001）。将对照LDL和硫醇化LDL（每毫升含0.2 mg蛋白质）与氧化还原活性铁（Fe(3+)；10 μmol/L）或作为阳性对照的铜（Cu(2+)；10 μmol/L）一起孵育。与其他人的观察结果一致，硫醇化降低了LDL中依赖Cu(2+)的脂质氧化产物的形成（在孵育6小时期间，硫醇化LDL中形成17±16 nmol/mg蛋白质，对照为81±21 nmol/mg蛋白质；P <.01）。然而，硫醇化对Fe(3+)介导的LDL氧化没有影响，在长时间孵育（长达48小时）期间脂质氧化产物基本上无法检测到。硫醇化对LDL（每毫升含0.2 mg蛋白质）被血红素复合铁（血红素；10 μmol/L）氧化同样没有影响，在孵育6小时期间，对照LDL和硫醇化LDL的脂质氧化产物分别增加至24±1和27±4 nmol/mg蛋白质（P>.05）。使用不同硫醇化程度（每毫克蛋白质含29±5、85±14、130±15和213±19 nmol硫醇）的LDL也观察到了类似结果。总之，这些结果表明硫醇化对LDL对铁介导氧化的敏感性没有影响。
