Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.36 (caspase-1)
 6,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proteolysis is a key feature of programmed cell death. Extracellular proteinases can activate cell surface receptors which trigger apoptosis, and the effector machinery requires the activation and activity of numerous intracellular proteinases (primarily caspases). Effective control of proteolysis is essential for homeostasis and can occur at two levels: regulation of proteinase activation, and regulation of the activated proteinase. Serpins control activated proteinases and several have been implicated in the regulation of cell death. Serpins that inhibit intracellular processes include the viral proteins CrmA and SPI-1, as well as the granzyme B inhibitor, PI-9. Another endogenous serpin, PN-I, prevents the delivery of an apoptotic signal by inhibiting an extracellular proteinase from cleaving a cell surface receptor. There is evidence to suggest that PAI-2 may target an extracellular as well as an intracellular proteinase. Much of our knowledge of proteolysis within apoptotic cells has come from studies using the poxvirus serpin CrmA/SPI-2. CrmA prevents cytokine processing by inhibiting caspase-1, and protects against Fas-, TNF- and TRAIL-mediated apoptosis by inhibiting an unidentified proteinase specific to these pathways. Work with CrmA has also clearly demonstrated that there are separable effector mechanisms within cells, and that those triggered by growth factor withdrawal, matrix dissociation or cytotoxic ligands are different in several respects to those triggered by radiation, chemicals or steroid hormones. It is likely that analysis of other poxvirus serpins with different inhibitory profiles (especially SPI-1) will yield further insights into these processes. Prospecting for intracellular serpin genes in other virus species may also be fruitful. Finally, all of the serpins known to regulate intracellular proteolysis are members of the ovalbumin subgroup. It remains to be seen whether the more recently described "orphan" ovalbumin serpins (Riewald and Schleef 1995; Sprecher et al. 1995; Sun et al. 1997) also have roles in the regulation of cell death.
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PMID:Serpins and regulation of cell death. 994 32

Inflammatory bladder disorders such as interstitial cystitis (IC) deserve attention since a major problem of the disease is diagnosis. IC affects millions of women and is characterized by severe pain, increased frequency of micturition, and chronic inflammation. Characterizing the molecular fingerprint (gene profile) of IC will help elucidate the mechanisms involved and suggest further approaches for therapeutic intervention. Therefore, in the present study we used established animal models of cystitis to determine the time course of bladder inflammatory responses to antigen, Escherichia coli lipopolysaccharide (LPS), and substance P (SP) by morphological analysis and cDNA microarrays. The specific aim of the present study was to compare bladder inflammatory responses to antigen, LPS, and SP by morphological analysis and cDNA microarray profiling to determine whether bladder responses to inflammation elicit a specific universal gene expression response regardless of the stimulating agent. During acute bladder inflammation, there was a predominant infiltrate of polymorphonuclear neutrophils into the bladder. Time-course studies identified early, intermediate, and late genes that were commonly up-regulated by all three stimuli. These genes included: phosphodiesterase 1C, cAMP-dependent protein kinase, iNOS, beta-NGF, proenkephalin B and orphanin, corticotrophin-releasing factor (CRF) R, estrogen R, PAI2, and protease inhibitor 17, NFkB p105, c-fos, fos-B, basic transcription factors, and cytoskeleton and motility proteins. Another cluster indicated genes that were commonly down-regulated by all three stimuli and included HSF2, NF-kappa B p65, ICE, IGF-II and FGF-7, MMP2, MMP14, and presenilin 2. Furthermore, we determined gene profiles that identify the transition between acute and chronic inflammation. During chronic inflammation, the urinary bladder presented a predominance of monocyte/macrophage infiltrate and a concomitant increase in the expression of the following genes: 5-HT 1c, 5-HTR7, beta 2 adrenergic receptor, c-Fgr, collagen 10 alpha 1, mast cell factor, melanocyte-specific gene 2, neural cell adhesion molecule 2, potassium inwardly-rectifying channel, prostaglandin F receptor, and RXR-beta cis-11-retinoic acid receptor. We conclude that microarray analysis of genes expressed in the bladder during experimental inflammation may be predictive of outcome. Further characterization of the inflammation-induced gene expression profiles obtained here may identify novel biomarkers and shed light into the etiology of cystitis.
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PMID:Gene expression profiling of mouse bladder inflammatory responses to LPS, substance P, and antigen-stimulation. 1205 14