Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.64 (proteinase K)
 4,071 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

LPS-stimulated macrophages release soluble factors that inhibit HIV-1 infection in both CD4(+) T lymphocytes and macrophages. These inhibitory factors include the CCR5 ligands RANTES, MIP-1alpha and MIP-1beta, which selectively block R5 HIV-1 strains, and a still unidentified factor with activity against X4 HIV-1 strains that we designate soluble macrophage-derived anti-HIV factor (MDAF). Here, we used X4 HIV-1 strains as specific probes to investigate the biological and physical characteristics of MDAF without the confounding effect of CCR5-binding chemokines. We show that MDAF has a broad spectrum of action, as it blocks infection by HIV-1 strains of different genetic subtypes. MDAF is sensitive to heat and proteinase K treatment, and it appears to be preformed within MDM, in that it is rapidly released upon LPS stimulation and its production is insensitive to cycloheximide, an inhibitor of protein neosynthesis. The convergent results of different assays indicate that MDAF acts primarily at the level of viral entry. Finally, MDAF is distinct from several known cytokines that possess anti-HIV-1 activity, including IL-10, IL-12, IL-16, IFN-gamma and alpha-defensins. The biological and physical characterization of MDAF may be instrumental in devising effective new strategies for its identification.
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PMID:Biological and physical characterization of the X4 HIV-1 suppressive factor secreted by LPS-stimulated human macrophages. 1944 59

In separate studies, an extract of soluble intracellular contents from whole bone marrow cells, named "Bone Marrow (BM) Soup", was reported to either improve cardiac or salivary functions post-myocardial infarction or irradiation (IR), respectively. However, the active components in BM Soup are unknown. To demonstrate that proteins were the active ingredients, we devised a method using proteinase K followed by heating to deactivate proteins and for safe injections into mice. BM Soup and "deactivated BM Soup" were injected into mice that had their salivary glands injured with 15Gy IR. Control mice received either injections of saline or were not IR. Results at week 8 post-IR showed the 'deactivated BM Soup' was no better than injections of saline, while injections of native BM Soup restored saliva flow, protected salivary cells and blood vessels from IR-damage. Protein arrays detected several angiogenesis-related factors (CD26, FGF, HGF, MMP-8, MMP-9, OPN, PF4, SDF-1) and cytokines (IL-1ra, IL-16) in BM Soup. In conclusion, the native proteins (but not the nucleic acids, lipids or carbohydrates) were the therapeutic ingredients in BM Soup for functional salivary restoration following IR. This molecular therapy approach has clinical potential because it is theoretically less tumorigenic and immunogenic than cell therapies.
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PMID:Identification of the active components in Bone Marrow Soup: a mitigator against irradiation-injury to salivary glands. 2652 54