Vitamin E isoforms differentially regulate intercellular adhesion molecule-1 activation of PKCα in human microvascular endothelial cells.
Vitamin E isoforms differentially regulate intercellular adhesion molecule-1 activation of PKCα in human microvascular endothelial cells.
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维生素E同工型在人类微血管内皮细胞中差异调节PKCα的细胞间粘附分子-1。
DOI：
10.1371/journal.pone.0041054
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Cook-Mills JM
中科院分区：
文献类型：
--
作者：
Abdala-Valencia H;Berdnikovs S;Cook-Mills JM
ICAM-1-dependent leukocyte recruitment in vivo is inhibited by the vitamin E isoform d-α-tocopherol and elevated by d-γ-tocopherol. ICAM-1 is reported to activate endothelial cell signals including protein kinase C (PKC), but the PKC isoform and the mechanism for ICAM-1 activation of PKC are not known. It is also not known whether ICAM-1 signaling in endothelial cells is regulated by tocopherol isoforms. We hypothesized that d-α-tocopherol and d-γ-tocopherol differentially regulate ICAM-1 activation of endothelial cell PKC. ICAM-1 crosslinking activated the PKC isoform PKCα but not PKCβ in TNFα-pretreated human microvascular endothelial cells. ICAM-1 activation of PKCα was blocked by the PLC inhibitor U73122, ERK1/2 inhibitor PD98059, and xanthine oxidase inhibitor allopurinol. ERK1/2 activation was blocked by inhibition of XO and PLC but not by inhibition of PKCα, indicating that ERK1/2 is downstream of XO and upstream of PKCα during ICAM-1 signaling. During ICAM-1 activation of PKCα, the XO-generated ROS did not oxidize PKCα. Interestingly, d-α-tocopherol inhibited ICAM-1 activation of PKCα but not the upstream signal ERK1/2. The d-α-tocopherol inhibition of PKCα was ablated by the addition of d-γ-tocopherol. Crosslinking ICAM-1 stimulated XO/ROS which activated ERK1/2 that then activated PKCα. ICAM-1 activation of PKCα was inhibited by d-α-tocopherol and this inhibition was ablated by the addition of d-γ-tocopherol. These tocopherols regulated ICAM-1 activation of PKCα without altering the upstream signal ERK1/2. Thus, we identified a mechanism for ICAM-1 activation of PKC and determined that d-α-tocopherol and d-γ-tocopherol have opposing regulatory functions for ICAM-1-activated PKCα in endothelial cells.
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影响因子：
4.4
作者：
Carman, CV;Jun, CD;Springer, TA
通讯作者：
Springer, TA
影响因子：
4.2
作者：
Azzi, A;Breyer, I;Zingg, JM
通讯作者：
Zingg, JM
影响因子：
1.7
作者：
Du, Chun-Ling;Xu, Yong-Jian;Qiao, Li-Fen
通讯作者：
Qiao, Li-Fen
影响因子：
64.8
作者：
ANDERSON, NG;MALLER, JL;STURGILL, TW
通讯作者：
STURGILL, TW
DOI：
10.4049/jimmunol.171.4.2099
发表时间：
2003-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Greenwood J;Amos CL;Walters CE;Couraud PO;Lyck R;Engelhardt B;Adamson P
通讯作者：
Adamson P