Seidner S R, Jobe A H, Ikegami M, Pettenazzo A, Priestley A, Ruffini L
Department of Pediatrics, Harbor-UCLA Medical Center, UCLA School of Medicine, Torrance 90509.
Biochim Biophys Acta. 1988 Aug 12;961(3):328-36. doi: 10.1016/0005-2760(88)90080-x.
Tracer quantities of 3H-labeled lysoPC and 32P-labeled natural rabbit surfactant were given intratracheally via a bronchoscope and [14C]palmitate was given intravenously to 25 rabbits with labeled PC and lysoPC measured in the alveolar wash, lung homogenate, lamellar bodies and microsomes at five times from 10 min to 6 h after tracheal injection. Surprisingly, only 31% of the administered lysoPC remained in its original form in the total lungs (alveolar wash + lung homogenate) by 10 min, of which 77% was in the alveolar wash. Meanwhile, by 10 min an additional 37% was already converted to PC, of which more than 98% was in the lung homogenate. LysoPC continued to be rapidly and efficiently converted to PC, with 62% conversion measured at 3 h. The converted lysoPC initially appeared with high specific activity in microsomes, then in lamellar bodies, and finally in the alveolar wash. The intravascular palmitate labeled lung PC had similar specific activity-time profiles in the subcellular fractions, while intratracheally administered natural rabbit surfactant had a constantly low specific activity in microsomes and much higher specific activities in lamellar bodies and alveolar wash. Another 25 rabbits received intratracheal lysoPC labeled in both the choline and palmitate moieties and then were studied from 1 to 24 h after tracheal injection. The ratio of the palmitate to choline labels indicated uptake and conversion to PC primarily by direct acylation rather than transacylation and by intact reuptake and conversion rather than breakdown and resynthesis. LysoPC is an attractive 'metabolic probe' of surfactant metabolism which undergoes very rapid and efficient intracellular conversion to PC via a subcellular pathway that parallels the remodeling and de novo synthetic pathways.
通过支气管镜将微量的³H标记的溶血磷脂酰胆碱(lysoPC)和³²P标记的天然兔表面活性剂经气管内给予25只兔子,并将[¹⁴C]棕榈酸盐经静脉给予。在气管内注射后10分钟至6小时的五个时间点,对肺泡灌洗液、肺匀浆、板层小体和微粒体中的标记PC和溶血磷脂酰胆碱进行测量。令人惊讶的是,到10分钟时,在全肺(肺泡灌洗液 + 肺匀浆)中,仅31%的给予的溶血磷脂酰胆碱保持其原始形式,其中77%在肺泡灌洗液中。与此同时,到10分钟时,另外37%已经转化为PC,其中超过98%在肺匀浆中。溶血磷脂酰胆碱继续快速且有效地转化为PC,在3小时时测得转化率为62%。转化后的溶血磷脂酰胆碱最初在微粒体中具有高比活性出现,然后在板层小体中,最后在肺泡灌洗液中。血管内棕榈酸盐标记的肺PC在亚细胞组分中具有相似的比活性 - 时间曲线,而经气管内给予的天然兔表面活性剂在微粒体中具有持续较低的比活性,在板层小体和肺泡灌洗液中具有高得多的比活性。另外25只兔子接受了在胆碱和棕榈酸部分均标记的气管内溶血磷脂酰胆碱,然后在气管内注射后1至24小时进行研究。棕榈酸盐与胆碱标记的比率表明,摄取并转化为PC主要是通过直接酰化而非转酰化,以及通过完整的再摄取和转化而非分解和再合成。溶血磷脂酰胆碱是表面活性剂代谢的一种有吸引力的“代谢探针”,它通过与重塑和从头合成途径平行的亚细胞途径在细胞内非常快速且有效地转化为PC。