Related Experiment Video

Updated: Jun 23, 2026

Deacetylation Assays to Unravel the Interplay between Sirtuins (SIRT2) and Specific Protein-substrates
14:32

Deacetylation Assays to Unravel the Interplay between Sirtuins (SIRT2) and Specific Protein-substrates

Published on: February 27, 2016

A protein deacetylase SIRT1 is a negative regulator of metalloproteinase-9

Yuji Nakamaru1, Chaitanya Vuppusetty, Hiroo Wada

  • 1Airway Disease Section, National Heart and Lung Institute, Imperial College, London, UK.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|April 21, 2009
PubMed

Insights

Reduced SIRT1 (a protein deacetylase) levels increase MMP9 expression, contributing to chronic obstructive pulmonary disease (COPD) pathogenesis. SIRT1 activation may offer a novel therapeutic strategy for inflammatory diseases.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Pulmonary Medicine

Background:

  • Matrix metalloproteinase-9 (MMP9) elevation is implicated in chronic obstructive pulmonary disease (COPD) pathogenesis.
  • The precise molecular mechanisms driving increased MMP9 expression in COPD remain incompletely understood.

Purpose of the Study:

  • To elucidate the molecular mechanism responsible for elevated MMP9 expression.
  • To investigate the role of SIRT1 in regulating MMP9 expression in the context of oxidative stress and COPD.

Main Methods:

  • Utilized human monocytic U937 cells and primary sputum macrophages.
  • Employed techniques including RT-PCR, Western blot, activity assays, and zymography.
  • Investigated SIRT1 and MMP9 levels in lung tissues from COPD patients and mice exposed to cigarette smoke.

Main Results:

  • SIRT1 inhibition or knockdown increased MMP9 expression, while SIRT1 activation by SRT2172 reduced MMP9 levels.
  • SIRT1 levels were decreased in COPD lungs, inversely correlating with MMP9 expression and promoter activation.
  • Oxidative stress (H2O2) and cigarette smoke reduced SIRT1 expression and activity, leading to elevated MMP9.

Conclusions:

  • SIRT1 acts as a negative regulator of MMP9 expression.
  • SIRT1 activation represents a potential therapeutic avenue for treating inflammatory conditions characterized by high MMP9 levels, such as COPD.

Related Concept Videos

Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult body.
A...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...