Abstract:
:Transforming growth factor β1 (TGF-β1) induces Mv1Lu cell senescence through inactivating glycogen synthase kinase 3 (GSK3), thereby inactivating complex IV and increasing intracellular ROS. In the present study, we identified protein kinase C delta (PKCδ) as an upstream regulator of GSK3 inactivation in this mechanism of TGF-β1-induced senescence. When Mv1Lu cells were exposed to TGF-β1, PKCδ phosphorylation simultaneously increased with GSK3 phosphorylation, and then AKT and ERK were phosphorylated. AKT phosphorylation and Smad signaling were independent of GSK3 phosphorylation, but ERK phosphorylation was downstream of GSK3 inactivation. TGF-β1-triggered GSK3 phosphorylation was blocked by inhibition of PKCδ, using its pharmacological inhibitor, Rottlerin, or overexpression of a dominant negative PKCδ mutant, but GSK3 inhibition with SB415286 did not alter PKCδ phosphorylation. Activation of PKCδ by PMA delayed cell growth and increased intracellular ROS level, but did not induce senescent phenotypes. In addition, overexpression of wild type or a constitutively active PKCδ mutant was enough to delay cell growth and decrease the mitochondrial oxygen consumption rate and complex IV activity, but weakly induce senescence. However, PMA treatment on Mv1Lu cells, which overexpress wild type and constitutively active PKCδ mutants, effectively induced senescence. These results indicate that PKCδ plays a key role in TGF-β1-induced senescence of Mv1Lu cells through the phosphorylation of GSK3, thereby triggering mitochondrial complex IV dysfunction and intracellular ROS generation.
journal_name
Free Radic Resjournal_title
Free radical researchauthors
Byun HO,Jung HJ,Kim MJ,Yoon Gdoi
10.3109/10715762.2014.929120subject
Has Abstractpub_date
2014-09-01 00:00:00pages
1100-8issue
9eissn
1071-5762issn
1029-2470journal_volume
48pub_type
杂志文章abstract::The use of antioxidants to prevent intracellular free radical damage is an area currently attracting considerable research interest. The compound 2',7'-dichlorofluorescin diacetate (DCFH-DA) is a probe for intracellular peroxide formation commonly used in such studies. During our studies we unexpectedly found that inc...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715769709097782
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journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715769709065764
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journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715769509065268
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journal_title:Free radical research
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journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715760100300231
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更新日期:2017-10-01 00:00:00
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journal_title:Free radical research
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journal_title:Free radical research
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journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715760000300601
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journal_title:Free radical research
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abstract::Thioredoxin-1 (TRX) is a redox-active protein with anti-inflammatory effects. This study investigated the optimal delivery method and the mechanisms of recombinant human TRX (rhTRX) to suppress neutrophil recruitment in a rat bleomycin (BLM)-induced sustained acute lung injury model. In male Wister rats intratracheall...
journal_title:Free radical research
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journal_title:Free radical research
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journal_title:Free radical research
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doi:10.1080/10715760100301391
更新日期:2001-12-01 00:00:00
abstract::The translocation of transcription factor EB (TFEB) to the nucleus plays a pivotal role in the regulation of basic cellular processes, such as lysosome biogenesis and autophagy. Autophagy is an intracellular degradation system that delivers cytoplasmic constituents to the lysosome, which is important in maintaining ce...
journal_title:Free radical research
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更新日期:2020-07-28 00:00:00
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journal_title:Free radical research
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journal_title:Free radical research
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journal_title:Free radical research
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journal_title:Free radical research
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更新日期:2019-01-01 00:00:00
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journal_title:Free radical research
pub_type: 杂志文章,评审
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更新日期:2011-08-01 00:00:00
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journal_title:Free radical research
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journal_title:Free radical research
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