Enzymatic basis for bioenergetic differences of alveolar versus peritoneal macrophages and enzyme regulation by molecular O2.

Enzymatic basis for bioenergetic differences of alveolar versus peritoneal macrophages and enzyme regulation by molecular O2.
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肺泡与腹膜巨噬细胞生物能差异的酶学基础以及分子 O2 的酶调节。

DOI:
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发表时间:
1977
影响因子:
15.9
通讯作者:
J. Theodore
J. Theodore
中科院分区:
医学1区
文献类型:
--
作者:
L. M. Simon;E. Robin;J. R. Phillips;J. Acevedo;S. G. Axline;J. Theodore

文献摘要

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肺泡巨噬细胞(AM)和腹腔巨噬细胞(PM)起源于共同的前体细胞,但在不同的O2环境中发挥作用。在目前的研究中,不同的O2张力对细胞代谢的影响已被定量测定,这些差异的酶的基础上建立,和一种机制,调节酶的差异证明。比较了兔AM和PM在空气和氮气中的O2消耗和乳酸产生。在空气中,AM表现出显著更高的O2利用率。在氮中(糖酵解是能量供应的主要来源),PM中的乳酸盐产量是其2 - 3倍。AM和PM中能量代谢的几种酶的比较表明,细胞能量学差异的一个基础是氧化磷酸化和糖酵解序列的关键酶活性的差异。将培养的AM暴露于缺氧条件导致这些酶的活性变化,使得AM非常类似于PM。氧化磷酸化中的一种关键酶(细胞色素氧化酶)显示活性降低,并达到与PM中发现的值相似的值。糖酵解中的一种关键酶(丙酮酸激酶)显示出增加的活性,其值与PM中发现的值相似。这些酶模式的改变发生在分离的细胞系统中,表明分子O2改变了能量代谢的某些酶的内在细胞调节。氧张力的改变可能导致氧化磷酸化和糖酵解中关键酶的生物合成速率和(或)生物降解速率的改变。反过来,酶模式的改变导致更合适的生物能量模式作为O2可用性的函数。
Alveolar macrophages (AM) and peritoneal macrophages (PM) originate from common precursor cells, but function in different O2 environments. In the present studies, the impact of different O2 tensions on cell metabolism has been quantitatively determined, an enzymatic basis for these differences established, and a mechanism which regulates enzymatic differences demonstrated. O2 consumption and lactate production were compared in rabbit AM and PM in air and nitrogen. In air, AM demonstrate significantly greater O2 utilization. In nitrogen, (where glycolysis is the major source of energy provision) lactate production is two- to threefold greater in the PM. A comparison of several enzymes of energy metabolism in AM and PM indicate that one basis for the differences in cell energetics is a difference in activity of key enzymes of both the oxidative phosphorlyative and the glycolytic sequences. Exposure of cultivated AM to hypoxic conditions results in changes in the activity of these enzymes such that the AM closely resembles the PM. A key enzyme in oxidative phosphorylation (cytochrome oxidase) shows decreased activity and reaches values similar to those found in the PM. A key enzyme in glycolysis (pyruvate kinase) shows increased activity to values resembling those found in the PM. These alterations in enzyme pattern occur in isolated cell systems, suggesting that molecular O2 modifies the intrinsic cellular regulation of some enzymes of energy metabolism. Alterations in O2 tension may lead to alterations of the rate of biosynthesis and (or) the rate of biodegradation of key enzymes involved in oxidative phosphorylation and glycolysis. In turn, the alteration of enzyme patterns leads to a more suitable bioenergetic pattern as a function of O2 availability.