Disease relevance of Antipain

• A protease inhibitor blocks SOS functions in Escherichia coli: antipain prevents lambda repressor inactivation, ultraviolet mutagenesis, and filamentous growth [1].
• Furthermore, antipain inhibits thermal induction of lambda prophage in the tif-1 mutant without affecting the kinetics of thermal induction of lambdacI857 prophage [1].
• We also showed that the processing protease activity for hHGF was suppressed by such serine protease inhibitors as leupeptin, antipain, and aprotinin, and that sera of patients with liver diseases such as fulminant hepatic failure, acute hepatitis, chronic hepatitis, and cirrhosis contained not only pro-hHGF but also the protease [2].
• The combination of antipain (20 mg/kg), leupeptin (40 mg/kg) and pepstatin (5 mg/kg) suppressed proteolysis almost completely at both 15 minutes (-88%, p less than 0.001) and at 6 hours (-72%, p less than 0.05) of ischemia, that is, throughout the development of irreversible injury [3].
• Iodoacetamide, calpain inhibitor 1, and antipain inhibited poliovirus 2Apro [4].

High impact information on Antipain

• Chromatid exchanges increased 26 hr posttreatment with the combination of MNNG and antipain used for transformation [5].
• DNA replication relative to untreated controls is not affected by MNNG, antipain, or the combination of the two; no synergistic lethality of antipain and MNNG occurred as reflected in the cloning efficiency [5].
• These results suggest that the protease inhibitor antipain has more than one mechanism of action in modulating the fixation and expression of transformation by x-irradiation, possibly by the modification of DNA repair [6].
• Using cultured normal hamster embryo cells and the heterploid mouse C3H cell line 10T1/2, clone 8, we have studied the effect of the protease inhibitor antipain on x-ray-induced neoplastic transformation [6].
• We found in both cell systems that, while there was no effect on cell survival as compared to irradiated controls, the addition of antipain at a concentration of 6 microgram/ml to the cultures 24 hr prior to irradiation resulted in enhanced transformation as compared to the frequency in cultures exposed to radiation alone [6].

Chemical compound and disease context of Antipain

• Because previous studies postulated that antipain could affect the induction of chromosomal aberrations by suppressing free radical reactions within cells, we also tested whether antipain affects X-ray-induced aberrations when present only during the time of irradiation, as is the case for free radical scavengers, such as L-cysteine [7].
• Effects of antipain (a protease inhibitor) on respiration, viability, and excision of pyrimidine dimers in UV-irradiated Escherichia coli cells [8].
• Leupeptin and antipain induced the appearance of microvillar extensions and blebs on the cytoplasmic membrane, resembling a shedding process [9].
• (c) Pre-incubation of the parasites with the proteinase inhibitors antipain and chymostatin, previously shown to confer protection from Leu-OMe toxicity, nearly completely prevented the morphological changes of megasomes [10].
• Antipain also prevented the suppression of UV-mutagenicity by HuIFN-alpha in RSa and xeroderma pigmentosum-derived fibroblast cells, as shown by culturing cells in medium containing antipain immediately after UV exposure and evaluating the generation of clones resistant to ouabain- or 6-thioguanine-mediated cytotoxicity [11].

Biological context of Antipain

• We found that 0.5 mM antipain (which has no effect on cell growth, overall RNA and protein synthesis, or induction of beta-galactosidase) drastically decreases mutagenesis [1].
• To test this hypothesis, we investigated the effect of a protease inhibitor, antipain [(1-carboxy-2-phenylethyl)carbamoyl-L-arginyl-L-valylargininal], on SOS induction [1].
• Antipain also blocks expression of thermally induced mutator activity (another manifestation of SOS repair) and filamentous growth in a tif-1 mutant that expresses SOS functions at 42 degrees without inhibition of DNA synthesis or detectable DNA damage [1].
• Antipain-induced suppression of oncogene expression in H-ras-transformed NIH3T3 cells [12].
• However, the full effect was observed when antipain was added at the subculture step on day 3 and during the subsequent cell proliferation [13].

Anatomical context of Antipain

• Elevation of antipain-sensitive protease activity was found, furthermore, in RSa cells cultured with HuIFN-alpha and subsequently treated with sodium saccharin [14].
• Under these conditions, cleavage can be blocked with 1-chloro-3-tosylamido-7-amino-L-2-heptanone and antipain, but protease inhibitors do not affect the inhibition of DNA binding that occurs in whole cytosol [15].
• Opioid receptors mediate antipain responses in both the peripheral nervous system and CNS [16].
• To determine whether future studies on the effects of proteolytic inhibition on infarct size are feasible, the ability of the proteinase inhibitors antipain, leupeptin, pepstatin and chymostatin, given in vivo, to interfere with proteolysis in ischemic myocardium was also evaluated [3].
• Plasminogen activator (PA) activity was analyzed in normal and transformed 10T1/2 mouse fibroblasts treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and the protease inhibitors antipain, leupeptin, and soybean trypsin inhibitor (SBTI) [17].

Associations of Antipain with other chemical compounds

• The protease inhibitors leupeptin and antipain were able to block (at least in part) the endogenous proteolysis and the necrotic process, but exhibited no effect on apoptosis and DNA fragmentation [18].
• Five other protease inhibitors, antipain, leupeptin, pepstatin, aprotinin, and soybean trypsin inhibitor, also suppressed TPA induction of transglutaminase activity [19].
• Although inhibitors of cathepsin B (leupeptin, antipain, N alpha-p-tosyl-L-lysine chloromethyl ketone, and chymostatin) were able to inhibit the release of monoiodotyrosine from treated cells in a time- and concentration-dependent manner, they had little effect on the processing step that apparently inactivates 125I-EGF [20].
• The enzyme activity was completely inhibited by diisopropyl fluorophosphate, p-amidinophenylmethanesulfonyl fluoride, leupeptin, antipain, bovine pancreatic trypsin inhibitor, soybean trypsin inhibitor, and ovomucoid, indicating that the entrapped enzyme is a serine proteinase [21].
• The enzyme was also inhibited by trans-epoxysuccinyl-L-leucylamido(4-guanidino)butane (E-64), leupeptin, antipain, salivary histidine-rich protein (HRP-5), soybean trypsin inhibitor, and EDTA [22].

Gene context of Antipain

• IGFBP-3 proteolytic activity in postoperative sera was markedly inhibited by antipain, Na-p-tosyl-L-lysine chloromethyl ketone, phenylmethylsulfonylfluoride, aprotinin, o-phenanthroline, and EDTA, but not by leupeptin or N-tosyl-L-phenylalanine chloromethyl ketone [23].
• 7. The marked inhibitory effects of leupeptin, antipain and chymostatin suggest that cathepsin B and possibly cathepsin L participate in the degradation of 125I-labelled albumin in yolk sacs [24].
• The sera of 21-day pregnant (but not nonpregnant) rats degrade IGFBP-3 in vitro, and this degradation is prevented by the protease inhibitor antipain [25].
• On the other hand, U-V-7 cells showed UV-induced elevation of antipain-sensitive protease activity, but p53 transfectants did not [26].
• Specific inhibitors for cathepsin B (E64, leupeptin, antipain) suppressed its activity completely [27].

Analytical, diagnostic and therapeutic context of Antipain

• Calcium-activated protease (CAP) was purified from the cytosol fraction of homogenized human platelet concentrates using a combination of gel filtration chromatography and affinity chromatography on antipain aminohexyl-Sepharose and activated thiol-Sepharose 4B [28].
• A variety of treatment protocols have been studied where antipain was present before, during and at various times post-irradiation [29].
• The effects of inhibitors of Ca(2+)-dependent endopeptidases (antipain and leupeptin) on morphine analgesia, reinforcing properties of morphine and on the development of opiate physical dependence were studied [30].
• The inhibitors antipain, leupeptin, aprotinin, L-1-tosylamide-2-phenyl-ethyl chloromethyl ketone (TPCK), or N-alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK) reduced parasite invasion to 16-66% of control after treatment of cultured cells or sporozoites with 5- or 50-micrograms/ml concentrations of inhibitors in the culture medium [31].
• The estrogen receptor (ER) was separated from the cytoplasmic components of the cow uterus through successive gel filtrations of the cytosol in the presence of antipain, a protease inhibitor [32].

References