Satriano Joseph
University of California, San Diego, Department of Medicine, Division of Nephrology-Hypertension, San Diego, California 92161, USA.
Ann N Y Acad Sci. 2003 Dec;1009:34-43. doi: 10.1196/annals.1304.004.
In acute inflammatory responses, such as wound healing and glomerulonephritis, arginine is the precursor for production of the cytostatic molecule nitric oxide (NO) and the pro-proliferative polyamines. NO is an early phase response whereas increased generation of polyamines is requisite for the later, repair phase response. The temporal switch of arginine as a substrate for the inducible nitric oxide synthase (iNOS)/NO axis to arginase/ornithine decarboxylase (ODC)/polyamine axis is subject to regulation by inflammatory cytokines as well as interregulation by the arginine metabolites themselves. Herein we describe the capacity of another arginine pathway, the metabolism of arginine to agmatine by arginine decarboxylase (ADC), to aid in this interregulation. Agmatine is an antiproliferative molecule due to its suppressive effects on intracellular polyamine levels, whereas the aldehyde metabolite of agmatine is a potent inhibitor of iNOS. We propose that the catabolism of agmatine to its aldehyde metabolite may act as a gating mechanism at the transition from the iNOS/NO axis to the arginase/ODC/polyamine axis. Thus, agmatine has the potential to serve in the coordination of the early and repair phase pathways of arginine in inflammation.
在急性炎症反应中，如伤口愈合和肾小球肾炎，精氨酸是细胞抑制分子一氧化氮（NO）和促增殖多胺生成的前体。NO是早期反应，而多胺生成增加是后期修复阶段反应所必需的。精氨酸作为诱导型一氧化氮合酶（iNOS）/NO轴的底物向精氨酸酶/鸟氨酸脱羧酶（ODC）/多胺轴的时间转换受炎症细胞因子的调节以及精氨酸代谢产物自身的相互调节。在此我们描述了另一条精氨酸途径，即精氨酸通过精氨酸脱羧酶（ADC）代谢生成胍丁胺，在这种相互调节中的作用。胍丁胺是一种抗增殖分子，因其对细胞内多胺水平有抑制作用，而胍丁胺的醛代谢产物是iNOS的强效抑制剂。我们提出胍丁胺分解代谢为其醛代谢产物可能在从iNOS/NO轴过渡到精氨酸酶/ODC/多胺轴时起到一种门控机制的作用。因此，胍丁胺有潜力参与炎症中精氨酸早期和修复阶段途径的协调。
