Acrolein induces activation of the epidermal growth factor receptor of human keratinocytes for cell death
Acrolein induces activation of the epidermal growth factor receptor of human keratinocytes for cell death
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丙烯醛诱导人角质形成细胞表皮生长因子受体的激活导致细胞死亡
DOI：
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发表时间：
2001
影响因子：
4
通讯作者：
I. Nakashima
中科院分区：
文献类型：
--
作者：
K. Takeuchi;M. Kato;H. Suzuki;A. Akhand;Jianghong Wu;K. Hossain;T. Miyata;Yoshinari Matsumoto;Y. Nimura;I. Nakashima
丙烯醛是一种由脂质过氧化产生的高反应性甲醛，会影响皮肤并引起各种疾病。研究了人类角质形成细胞暴露于丙烯醛对细胞表面定向信号转导至细胞的影响。将人角质形成细胞与相对低浓度 (50 μM) 的丙烯醛一起孵育，在孵育开始后 5-30 分钟内，表皮生长因子受体 (EGFR) 酪氨酸磷酸化为 180 kDa 分子。这一早期事件之后，在孵化开始后 60-120 分钟期间，含磷酸酪氨酸的蛋白质的密度和数量增加。在体外激酶测定中，通过外源添加的底物酪蛋白的自磷酸化和磷酸化水平来测量EGFR的催化活性，在孵育开始后1分钟内大幅增加，然后在30分钟后逐渐下降。 MAP 家族激酶，包括 ERK、JNK 和 p38 激酶，以及潜在的下游转录因子 c-Jun 在 5-30 分钟内均被促进磷酸化/激活。 EGFR 选择性迅速磷酸化/激活，随后 MAP 家族激酶和 c-Jun 磷酸化，并被特定 EGFR 抑制剂 AG1478 阻断，表明 EGFR 激活是丙烯醛处理细胞中细胞内信号转导的主要（也可能是单一）细胞表面元件。将人角质形成细胞与 50 μM 丙烯醛一起孵育可诱导非典型细胞凋亡，其形态学凋亡特征为低级寡核苷大小的 DNA 碎片。通过与 AG1478 预孵育，部分抑制丙烯醛对人角质形成细胞的细胞病变作用，表明 EGFR 介导的信号通路参与非典型细胞凋亡。这些结果提供了关于丙烯醛诱导的细胞表面定向信号转导至人类角质形成细胞的新信息，这些信息可能有助于了解环境丙烯醛和产生丙烯醛的紫外线照射引起的许多皮肤疾病的发病机制。 J.细胞。生物化学。 81：679–688，2001。© 2001 Wiley-Liss, Inc.
Acrolein, which is a highly reactive formaldehyde generated by lipid peroxidation, can affect skin and cause various disorders. The effect of exposure of human keratinocytes to acrolein on cell surface‐oriented signal transduction into cells was examined. Incubation of human keratinocytes with a relatively low concentration (50 μM) of acrolein caused a prompt and selective induction of tyrosine phosphorylation of the epidermal growth factor receptor (EGFR) as a 180‐kDa molecule during the period from 5–30 min after the start of incubation. This early event was followed by an increase in the density and number of phosphotyrosine‐containing proteins during the period from 60–120 min after the start of incubation. The catalytic activity of EGFR as measured by the levels of autophorphorylation and phosphorylation of an exogenously added substrate, casein, in in vitro kinase assay, greatly increased as early as 1 min after the start of incubation and then decreased gradually 30 min later. MAP family kinases, including ERK, JNK, and p38 kinase, and the potentially downstream transcription factor c‐Jun were all promoted for phosphorylation/activation during a period of 5–30 min. Selective prompt phosphorylation/activation of EGFR followed by phosphorylation of MAP family kinases and c‐Jun and their blockade by a specific EGFR inhibitor, AG1478, suggested that activation of EGFR is the major, and possibly single, cell surface element for intracellular signal transduction in acrolein‐treated cells. Incubation of human keratinocytes with 50 μM of acrolein induced atypical apoptosis with morphologic apoptotic features with low‐grade oligonucleoside‐sized DNA fragmentation. Partial inhibition of such a cytopathic effect of acrolein on human keratinocytes by preincubation with AG1478 suggests the involvement of an EGFR‐mediated signal pathway for atypical apoptosis. These results provide new information on acrolein‐induced cell surface‐oriented signal transduction to human keratinocytes, and this information may be useful for understanding the pathogenesis of a number of skin diseases in response to environmental acrolein and acrolein‐generating ultraviolet irradiation. J. Cell. Biochem. 81: 679–688, 2001. © 2001 Wiley‐Liss, Inc.
DOI：
10.1073/pnas.80.5.1337
发表时间：
1983-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
KAWAMOTO, T;SATO, JD;MENDELSOHN, J
通讯作者：
MENDELSOHN, J
丙烯醛对人肺泡巨噬细胞 NF-κB 活性的影响。
DOI：
10.1152/ajplung.1999.277.3.l550
发表时间：
1999
期刊：
The American journal of physiology
影响因子：
--
作者：
Li,L;HamiltonJr,RF;Holian,A
通讯作者：
Holian,A