Miller A M, Sandler E, Kobb S M, Eastgate J, Zucali J
Division of Medical Oncology, College of Medicine, Gainesville, FL 32610.
Exp Hematol. 1993 Jan;21(1):9-15.
The enzyme gamma-glutamyl transferase (GGT) is a multifunctional enzyme that participates in a number of metabolic processes, including the conversion of leukotriene C4(LTC4) to leukotriene D4(LTD4). LTD4 is necessary for normal myeloid proliferation and differentiation. We have examined the ability of hematopoietic growth factors (HGF) to induce GGT enzyme activity and mRNA content in a HGF-responsive cell line (KG-1). Incubation of KG-1 with recombinant human cytokines interleukin-1 beta (IL-1 beta), interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor (TNF), but not interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF) or monocyte colony-stimulating factor (M-CSF), results in significant increases in GGT enzyme activity. The increases in GGT activity are both dose- and time-dependent. In response to IL-1, increases in enzyme activity are seen by 6 hours and activity is maximal by 24 hours. GGT mRNA increases also occur and peak by 3 to 6 hours. These results indicate that induction of increases in GGT mRNA levels and enzyme activity occur in myeloid cells in response to HGFs. This induction, together with the requirement for LTD4 for normal granulopoiesis, supports a role for GGT in the cellular events occurring in myeloid cells in response to HGFs.
γ-谷氨酰转移酶（GGT）是一种多功能酶，参与多种代谢过程，包括白三烯C4（LTC4）向白三烯D4（LTD4）的转化。LTD4是正常髓系增殖和分化所必需的。我们研究了造血生长因子（HGF）在HGF反应性细胞系（KG-1）中诱导GGT酶活性和mRNA含量的能力。用重组人细胞因子白细胞介素-1β（IL-1β）、白细胞介素-3（IL-3）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）和肿瘤坏死因子（TNF）孵育KG-1细胞，但不包括白细胞介素-6（IL-6）、粒细胞集落刺激因子（G-CSF）或单核细胞集落刺激因子（M-CSF），会导致GGT酶活性显著增加。GGT活性的增加具有剂量和时间依赖性。对IL-1的反应中，6小时时酶活性开始增加，24小时时活性达到最大值。GGT mRNA也会增加，并在3至6小时达到峰值。这些结果表明，髓系细胞中GGT mRNA水平和酶活性的增加是对HGFs的反应诱导产生的。这种诱导作用，连同正常粒细胞生成对LTD4的需求，支持了GGT在髓系细胞对HGFs反应中发生的细胞事件中的作用。
