These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Role of PKC-α in NF-κB-MT1-MMP-mediated activation of proMMP-2 by TNF-α in pulmonary artery smooth muscle cells.
    Author: Roy S, Chakraborti T, Chowdhury A, Chakraborti S.
    Journal: J Biochem; 2013 Mar; 153(3):289-302. PubMed ID: 23266860.
    Abstract:
    We sought to evaluate the mechanism(s) associated with pro matrix metalloprotease 2 (proMMP-2) activation in bovine pulmonary artery smooth muscle cells. Preincubation of cells with anti-TNFR1 antibody prevented tumour necrosis factor-α (TNF-α)-induced proMMP-2 activation and increase in membrane type 1 matrix metalloprotease (MT1-MMP) expression as well as inhibition of tissue inhibitor of metalloproteinase 2 (TIMP-2) expression, indicating the role of TNFR1 receptor during TNF-α stimulation. Anti-MT1-MMP antibody abrogated proMMP-2 activation by TNF-α-stimulated cell membrane, suggesting the involvement of MT1-MMP in proMMP-2 activation. Induction of MT1-MMP expression in response to TNF-α occurs via activation of nuclear factor (NF)-κB on inhibitory κB kinase (IKK) activation and subsequently phosphorylation/degradation of IκB-α. Inhibition of protein kinase C (PKC)-α activity by Go6976 and PKC-α siRNA prevented TNF-α-induced IKK activity, IκB-α phosphorylation/degradation and NF-κB activation. Inhibition of PKC-α activity also prevented TNF-α-induced MT1-MMP expression and proMMP-2 activation as well as down regulation of TIMP-2 expression. Inhibition of IκB-α phosphorylation by PS-1145, an IKK selective inhibitor, prevented TNF-α-induced increase in MT1-MMP expression and proMMP-2 activation, which although did not alter inhibition of TIMP-2 expression. Overall, we unravelled a hitherto unknown mechanism of the involvement of PKC-α in proMMP-2 activation and inhibition of TIMP-2 expression by NF-κB-MT1-MMP-dependent and -independent pathway, respectively, during TNF-α stimulation in pulmonary artery smooth muscle cells.
    [Abstract] [Full Text] [Related] [New Search]