Foley Timothy D, Petro Laura A, Stredny Coral M, Coppa Teresa M
Department of Chemistry, University of Scranton, 800 Linden St., Scranton, PA 18510, USA.
Neurochem Res. 2007 Nov;32(11):1957-64. doi: 10.1007/s11064-007-9394-x. Epub 2007 Jun 12.
A molecular basis for the inhibition of brain protein phosphatase 2A (PP2A) activity by oxidative stress was examined in a high-speed supernatant (HSS) fraction from rat cerebral cortex. PP2A activity was subject to substantial disulfide reducing agent-reversible inhibition in the HSS fraction. Results of gel electrophoresis support the conclusions that inhibition of PP2A activity was associated with the both the disulfide cross-linking of the catalytic subunit (PP2A(C)) of the enzyme to other brain proteins and with the formation of an apparent novel intramolecular disulfide bond in PP2A(C). Additional findings that the vicinal dithiol cross-linking reagent phenylarsine oxide (PAO) produced a potent dithiothreitol-reversible inhibition of PP2A activity suggest that the cross-linking of PP2A(C) vicinal thiols to form an intramolecular disulfide bond may be sufficient to inhibit PP2A activity under oxidative stress. We propose that the dithiol-disulfide equilibrium of a vicinal thiol pair of PP2A(C) may confer redox sensitivity on cellular PP2A.
在大鼠大脑皮层的高速上清液（HSS）组分中，研究了氧化应激抑制脑蛋白磷酸酶2A（PP2A）活性的分子基础。在HSS组分中，PP2A活性受到大量二硫键还原剂可逆性抑制。凝胶电泳结果支持以下结论：PP2A活性的抑制与该酶催化亚基（PP2A(C)）与其他脑蛋白的二硫键交联以及PP2A(C)中明显新形成的分子内二硫键的形成有关。另外的发现是，邻二硫醇交联试剂苯胂氧化物（PAO）对PP2A活性产生了有效的二硫苏糖醇可逆性抑制，这表明PP2A(C)的邻二硫醇交联形成分子内二硫键可能足以在氧化应激下抑制PP2A活性。我们提出，PP2A(C)的一对邻二硫醇的二硫醇 - 二硫键平衡可能赋予细胞PP2A氧化还原敏感性。
