Galvin R J, Ramp W K, Lenz L G
Department of Pharmacology, University of Louisville, Kentucky 40292.
Connect Tissue Res. 1991;26(3):217-29. doi: 10.3109/03008209109152440.
The effects of smokeless tobacco extract (STE) and prolyl hydroxylase inhibitors on protein synthesis by isolated osteoblast-like cells were compared. STE and 2,2'dipyridyl markedly inhibited alkaline phosphatase (Alpase) and [3H]proline hydroxylation without affecting glycolysis (lactate production). However, pyridine 2,5-dicarboxylate (2,5-PDC) did not inhibit [3H] proline hydroxylation, Alpase activity, or glycolysis at moderate concentrations. The [3H]hydroxyproline to [3H]proline ratio in the cell layers demonstrated a concentration-dependent decrease with increasing STE and inhibitor concentrations. In the cell layers, the collagenous protein (CP) content was decreased after exposure to STE, 2,2'dipyridyl, and 2,5-PDC and the noncollagenous protein (NCP) content was decreased after exposure to STE and 2,5-PDC. However, the effects on CP were at least twofold greater than on NCP. Similar results were observed regarding protein released to the culture medium. These data demonstrate that STE, like 2,2'dipyridyl, inhibits the hydroxylation of proline and the synthesis of collagenase-digestible protein.
比较了无烟烟草提取物（STE）和脯氨酰羟化酶抑制剂对分离的成骨样细胞蛋白质合成的影响。STE和2,2'-联吡啶显著抑制碱性磷酸酶（Alpase）和[3H]脯氨酸羟化，而不影响糖酵解（乳酸生成）。然而，吡啶2,5-二羧酸（2,5-PDC）在中等浓度下不抑制[3H]脯氨酸羟化、Alpase活性或糖酵解。细胞层中[3H]羟脯氨酸与[3H]脯氨酸的比率随STE和抑制剂浓度的增加呈浓度依赖性降低。在细胞层中，暴露于STE、2,2'-联吡啶和2,5-PDC后，胶原蛋白（CP）含量降低，暴露于STE和2,5-PDC后，非胶原蛋白（NCP）含量降低。然而，对CP的影响比对NCP的影响至少大两倍。关于释放到培养基中的蛋白质也观察到了类似的结果。这些数据表明，STE与2,2'-联吡啶一样，抑制脯氨酸的羟化和胶原酶可消化蛋白的合成。
