Lindheimer M, Montet JC, Zajac J, Lagerge S
Laboratoire des Agrégats Moléculaires et Matériaux Inorganiques, ESA 5072, Université Montpellier II, Place E. Bataillon CC 015, 34095 Cedex 05, Montpellier, France
Colloids Surf B Biointerfaces. 2001 Feb 1;20(2):119-127. doi: 10.1016/s0927-7765(00)00185-5.
Bile salts play a central role in the promotion of cytotoxicity or cytoprotection. In this study, we examined the interaction of different bile salts with egg lecithin vesicles using 31P NMR spectroscopy. The effects of taurochenodeoxycholate (TCDC or 3alpha,7alpha,-dihydroxy-5beta-cholanoyl taurine, of tauroursodeoxycholate (TUDC) or 3alpha,7beta,-dihydroxy-5beta-cholanoyl taurine) and of taurobetamuricholate (TbetaMC or 3alpha,6beta,7beta,-trihydroxy-5beta-cholanoyl taurine), at various bile salt/lecithin ratios, were evaluated. From the percent 31P present in vesicles, the micellar capacity of bile salts to dissolve lecithin was determined. TCDC was incorporated into vesicles for bile salt/lecithin molar ratios lower than 0.62 while for TUDC and TbetaMC, the critical ratios were 0.94 and 1.1, respectively. The 31P chemical shift change was markedly larger with TCDC than that found with TUDC and TbetaMC. In order to specify the low interactions observed between hydrophilic bile salts and lecithin, we determined the intermixed micellar/vesicular bile salt concentrations (IMVC) of bile salt/lecithin solutions using rapid ultrafiltration-centrifugation for TUDC and lecithin solubility measurements for TUDC, TbetaMC and TCDC. The low IMVC obtained indicate that even hydrophilic bile salts were bound mostly to the mixed aggregates. In conclusion, the low disturbance in the arrangement of lecithin induced by TUDC and TbetaMC appears to be due to the interfacial location of these bile salts. TCDC (7alpha OH) penetrates more deeply in the membrane than the 7beta hydroxylated bile salts that may partly explain the distinct damaging effects of these bile salts.
胆盐在促进细胞毒性或细胞保护方面发挥着核心作用。在本研究中,我们使用³¹P核磁共振光谱研究了不同胆盐与卵磷脂囊泡的相互作用。评估了牛磺鹅去氧胆酸盐(TCDC或3α,7α-二羟基-5β-胆酰牛磺酸)、牛磺熊去氧胆酸盐(TUDC或3α,7β-二羟基-5β-胆酰牛磺酸)和牛磺β-鼠胆酸盐(TβMC或3α,6β,7β-三羟基-5β-胆酰牛磺酸)在不同胆盐/卵磷脂比例下的作用。根据囊泡中³¹P的百分比,确定胆盐溶解卵磷脂的胶束能力。当胆盐/卵磷脂摩尔比低于0.62时,TCDC可掺入囊泡中,而对于TUDC和TβMC,临界比例分别为0.94和1.1。TCDC引起的³¹P化学位移变化明显大于TUDC和TβMC。为了明确亲水性胆盐与卵磷脂之间观察到的低相互作用,我们使用快速超滤离心法测定了胆盐/卵磷脂溶液的混合胶束/囊泡胆盐浓度(IMVC),并对TUDC进行了卵磷脂溶解度测量,对TUDC、TβMC和TCDC也进行了测量。获得的低IMVC表明,即使是亲水性胆盐也大多与混合聚集体结合。总之,TUDC和TβMC对卵磷脂排列的低干扰似乎是由于这些胆盐位于界面处。TCDC(7α-OH)比7β-羟基化胆盐更深入地穿透膜,这可能部分解释了这些胆盐不同的损伤作用。