Proapoptotic Effect of Proteolytic Activation of Matrix Metalloproteinases by<i>Streptococcus pyogenes</i>Thiol Proteinase (<i>Streptococcus</i>Pyrogenic Exotoxin B)

Tamura, Fumio; Nakagawa, Rumiko; Akuta, Teruo; Okamoto, Shigefumi; Hamada, Shigeyuki; Maeda, Hiroshi; Kawabata, Shigetada; Akaike, Takaaki

doi:10.1128/iai.72.8.4836-4847.2004

Cited by 55 publications

(53 citation statements)

References 61 publications

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“…Similarly, TACE and the insulin-like growth factor binding protein 6 (IGFBP-6) are inducers of apoptosis whereas IGF-1 inhibits apoptosis. TACE, a key enzyme (sheddase) that releases TNF-␣ from its inactive cell-bound precursor (119), has been shown to induce apoptosis in U937 cells via the release of TNF-␣ and soluble FasL (114).…”

Section: Discussionmentioning

confidence: 99%

Molecular Interactions of Human Immunodeficiency Virus Type 1 with Primary Human Oral Keratinocytes

Acheampong¹,

Parveen²,

Muthoga³

et al. 2005

J Virol

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Section: Discussionmentioning

confidence: 99%

Molecular Interactions of Human Immunodeficiency Virus Type 1 with Primary Human Oral Keratinocytes

Acheampong¹,

Parveen²,

Muthoga³

et al. 2005

J Virol

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“…Extrinsic apoptosis can be attributed in part to the activities of SpeB, which has been shown to activate matrix metalloproteinases on the surface of mammalian cells and trigger TNF-␣ and Fas ligand release (594). Alternatively, interactions of GAS with epithelial cells induce caspase-9 activation, cytochrome c release, and Bax translocation to the mitochondria (416,417).…”

Section: Host Cell Modulationmentioning

confidence: 99%

“…SpeB cysteine protease is a crucial virulence factor, which is able to modulate functions of S. pyogenes cell surface proteins in colonization and significantly contribute to tissue destruction in necrotizing fasciitis. SpeB can cleave host ECM proteins, e.g., Fn, as well as immune system components, e.g., the antimicrobial peptide cathelicidin LL-37, and activates matrix metalloproteinases to promote further tissue damage and the release of proapoptotic factors (594). SLO is a human-specific cytolysin (Table 2) with a range of properties, including the ability to form pores through which effector proteins, e.g., NAD ϩ glycohydrolase (SN), may be injected into the host cell cytoplasm (184).…”

Section: Virulence Factorsmentioning

confidence: 99%

StreptococcusAdherence and Colonization

Nobbs

Lamont

Jenkinson

2009

Microbiol Mol Biol Rev

552

569

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SUMMARY Streptococci readily colonize mucosal tissues in the nasopharynx; the respiratory, gastrointestinal, and genitourinary tracts; and the skin. Each ecological niche presents a series of challenges to successful colonization with which streptococci have to contend. Some species exist in equilibrium with their host, neither stimulating nor submitting to immune defenses mounted against them. Most are either opportunistic or true pathogens responsible for diseases such as pharyngitis, tooth decay, necrotizing fasciitis, infective endocarditis, and meningitis. Part of the success of streptococci as colonizers is attributable to the spectrum of proteins expressed on their surfaces. Adhesins enable interactions with salivary, serum, and extracellular matrix components; host cells; and other microbes. This is the essential first step to colonization, the development of complex communities, and possible invasion of host tissues. The majority of streptococcal adhesins are anchored to the cell wall via a C-terminal LPxTz motif. Other proteins may be surface anchored through N-terminal lipid modifications, while the mechanism of cell wall associations for others remains unclear. Collectively, these surface-bound proteins provide Streptococcus species with a “coat of many colors,” enabling multiple intimate contacts and interplays between the bacterial cell and the host. In vitro and in vivo studies have demonstrated direct roles for many streptococcal adhesins as colonization or virulence factors, making them attractive targets for therapeutic and preventive strategies against streptococcal infections. There is, therefore, much focus on applying increasingly advanced molecular techniques to determine the precise structures and functions of these proteins, and their regulatory pathways, so that more targeted approaches can be developed.

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“…Human ProMMP-9 was synthesized using a baculovirus system and purified by gelatin 4B column chromatography as described previously (16). Recombinant active MMP-9 and Snitroso-glutathione (GSNO) were purchased from Calbiochem.…”

Section: Experimental Procedures Materialsmentioning

confidence: 99%

Nitric Oxide Regulation of MMP-9 Activation and Its Relationship to Modifications of the Cysteine Switch

et al. 2008

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Matrix metalloproteases (MMPs) are Zn-containing endopeptidases involved in the degradation of extracellular matrix components and are typically secreted in a latent (pro-MMP) form and activated either by proteolytic or oxidative disruption of a conserved cysteine switch. Several recent studies have suggested that nitric oxide (NO) can contribute to the activation of MMPs, but the mechanisms involved are incompletely understood. We investigated the ability of NO to regulate the activation of (pro)MMP-9 using a variety of NO-donor compounds and characterized modifications of the cysteine switch using a synthetic peptide (PRCGVPDLGR) representing the cysteine switch domain of MMP-9. Among the NO-donors used, only S-nitrosocysteine (SNOC) was found to be capable of modest activation of proMMP-9, but S-nitrosoglutathione (GSNO) or the NONOates, DEA-NO, SPER-NO, or DETA-NO, were ineffective. In fact, high concentrations of DETA-NO were found to inhibit MMP-9 activity, presumably by direct interaction with the active-site Zn 2+ . Analysis of chemical modifications within the Cys-containing peptide, PRCGVPDLGR, revealed rapid and transient S-nitrosylation by SNOC and GSNO, and formation of mixed disulfides and dimerized peptide as major final products. Similarly, NONOates induced transient S-nitrosylation and primarily peptide dimerization. Coordination of the peptide Cys with a synthetic Zn 2+ complex, to more closely mimic the structure of the active site in proMMP-9, reduced peptide nitrosylation and oxidation by NONOates, but enhanced peptide nitrosylation by SNOC and GSNO. Collectively, our results demonstrate that NO is incapable of directly activating proMMP-9 and that S-nitrosylation of MMP-9 propeptide by NO-donors is unrelated to their ability to regulate MMP-9 activity.Matrix metalloproteinases (MMPs) comprise a family of zinc-containing endopeptidases and play important roles in development, inflammation, tissue injury and repair, and tumor biology (1,2). The MMP family consists of at least 26 members that share several structural characteristics including a highly conserved Cys-containing pro-peptide domain and a catalytic domain containing three His residues bound to a Zn(II) metal ion. MMPs are typically expressed at low levels in normal tissues, but in conditions of inflammation and/or tissue injury, MMP expression is generally increased by the action of pro-inflammatory † This work was supported by NIH research grants R01 HL074295 and R01 HL068865 (to A.vdV.), T32 ES07122 (training fellowship to S.M.M.), and P20 RR16462 (to the Vermont Genetics Network). Several recent studies have suggested that NO contributes to the activation of MMPs or related metalloproteinases by S-nitrosylation (often also referred to as S-nitrosation) of the pro-domain Cys residue. For example, MMP-9 activation in vivo was found to be associated with increased NOS activity, and the nitrosothiol S-nitrosocysteine is capable of activating pro-MMP-9 by a mechanism that appears to involve transnitrosylation (4,11). Similar...

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Proapoptotic Effect of Proteolytic Activation of Matrix Metalloproteinases byStreptococcus pyogenesThiol Proteinase (StreptococcusPyrogenic Exotoxin B)

Cited by 55 publications

References 61 publications

Molecular Interactions of Human Immunodeficiency Virus Type 1 with Primary Human Oral Keratinocytes

Molecular Interactions of Human Immunodeficiency Virus Type 1 with Primary Human Oral Keratinocytes

StreptococcusAdherence and Colonization

Nitric Oxide Regulation of MMP-9 Activation and Its Relationship to Modifications of the Cysteine Switch

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