The etiology of acrylamide neuropathy: enolase, phosphofructokinase, and glyceraldehyde-3-phosphate dehydrogenase activities in peripheral nerve, spinal cord, brain, and skeletal muscle of acrylamide-intoxicated cats.
The etiology of acrylamide neuropathy: enolase, phosphofructokinase, and glyceraldehyde-3-phosphate dehydrogenase activities in peripheral nerve, spinal cord, brain, and skeletal muscle of acrylamide-intoxicated cats.
复制标题
丙烯酰胺神经病的病因：丙烯酰胺中毒猫的周围神经、脊髓、大脑和骨骼肌中的烯醇化酶、磷酸果糖激酶和甘油醛-3-磷酸脱氢酶活性。
DOI：
10.1016/0041-008x(91)90235-7
复制
发表时间：
1981
影响因子：
3.8
通讯作者：
Howland,RD
中科院分区：
文献类型：
--
作者：
Howland,RD
以前的研究表明，神经毒素，丙烯酰胺，抑制几种糖酵解酶在体外测试时，神经元特异性烯醇化酶（NSE）的活性降低与神经毒性剂量的丙烯酰胺治疗的大鼠。为了确定对NSE的影响是否具有种属特异性，以及甘油醛-3-磷酸脱氢酶（GAPDH）和磷酸果糖激酶（PFK）活性是否在体内降低，用15或30 mg/kg/天的丙烯酰胺对猫进行了10天的处理。最后一次注射后24小时，测定坐骨神经、脑、脊髓和骨骼肌样品的总烯醇化酶、NSE、GAPDH和PFK活性。低剂量和高剂量丙烯酰胺分别导致以下NSE活性降低：远端周围神经中分别降低62.1%和69.7%，脑中分别降低37.1%和45.4%。GAPDH活性在大脑和坐骨神经的近端和远端部分中同样受到抑制。此外，所有其他组织均显示GAPDH显著降低。外周神经、脊髓和骨骼肌的总烯醇化酶活性和这些组织和脑中的PFK活性均未降低。相反，高剂量丙烯酰胺可使腓肠肌PFK增加700%，这可能是一种代偿机制。这些数据支持这一假设，即丙烯酰胺的毒性作用机制涉及抑制糖酵解在两个酶位点和毒性剂表现出的选择性驻留在其抑制神经元特异性同工酶的能力。
Previous studies have shown that the neurotoxin, acrylamide, inhibits several glycolytic enzymes when tested in vitro and that the activity of neuron-specific enolase (NSE) is decreased in rats treated with neurotoxic doses of acrylamide. To determine whether the effect on NSE was species specific and whether glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and phosphofructokinase (PFK) activities were decreased in vivo, cats were treated with either 15 or 30 mg/kg/day of acrylamide for 10 days. Twenty-four hours after the last injection, samples of sciatic nerve, brain, spinal cord, and skeletal muscle were assayed for total enolase, NSE, GAPDH, and PFK activities. The low and high doses of acrylamide resulted in the following respective decreases in NSE activity: 62.1 and 69.7% in the distal peripheral nerve and 37.1 and 45.4% in brain. GAPDH activity was similarly depressed in brain and both proximal and distal portions of the sciatic nerve. Additionally, all other tissues showed significant reductions in GAPDH. Neither total enolase activity of peripheral nerve, spinal cord, and skeletal muscle nor PFK activity in these tissues and in brain was decreased. In contrast, PFK in gastrocnemius muscle was increased 700% by the high dose of acrylamide, which may represent a compensatory mechanism. These data support the hypothesis that the mechanism of the toxic action of acrylamide involves inhibition of glycolysis at two enzymatic sites and that the selectivity exhibited by the toxic agent resides in its ability to inhibit a neuron-specific isoenzyme.