Disease relevance of Allnal

• Treatment of OM10.1 cells latently infected with human immunodeficiency virus type 1 (HIV-1) with phorbol ester and calcium ionophore (A23187) induced virus replication which was blocked by N-Ac-Leu-Leu-norleucinal (ALLnL), a calpain inhibitor I, and not by lactacystin, a specific proteasome inhibitor [1].

High impact information on Allnal

• To test this idea, we investigated whether peptide aldehyde inhibitors of the proteasome, N-acetyl-leucyl-leucyl-norleucinal (LLN), or the more potent CBZ-leucyl-leucyl-leucinal (MG132) suppressed proteolysis in incubated rat skeletal muscles [2].
• Annexin VI-dependent budding is accompanied by the loss of approximately 50% of the spectrin from the membrane and is blocked by the cysteine protease inhibitor N-acetyl-leucyl-leucyl-norleucinal (ALLN) [3].
• In addition, pretreatment of the cells with the proteasome inhibitor N-Ac-Leu-Leu-norleucinal inhibits this ligand-induced degradation and, in agreement with previous studies, stabilizes a hyperphosphorylated form of the human I kappa B alpha protein [4].
• Indeed, rapamycin decreases the half-life of cyclin D1 protein, and the rapamycin-induced decrease in cyclin D1 levels is partially abrogated by proteasome inhibitor N-acetyl-leucyl-leucyl-norleucinal [5].
• Calpain inhibitor N-acetyl-leucyl-leucyl-norleucinal blocked FAK cleavage, cell adhesion, and micromotion [6].

Biological context of Allnal

• Further evidence that nucleotide hydrolysis is not coupled to peptide bond cleavage was obtained using N-acetyl-leucyl-leucyl-norleucinal (LLnL) [7].
• Downregulation of ERG25 by LDL was abolished by an inhibitor of neutral cysteine proteases (N-acetyl-leucyl-leucyl-norleucinal) that abrogates SREBP catabolism [8].
• Inhibition experiments using the calpain inhibitor N-acetyl-leucyl-leucyl-norleucinal suggested that calpains are involved in reovirus-mediated pIgR upregulation [9].
• Calpain inhibitors Cbz-Val-Phe-H (MDL28170, 20muM) and N-acetyl-leucyl-leucyl-norleucinal (ALLN, 20muM) increased the levels of dephosphorylated p120-catenin, aggregation, and cell survival as detected by reduced LDH release in ischemic cells [10].
• Since degradation of the stably expressed K 417 ochre was not inhibited by lactacystin, leupeptin, NH(4)Cl, or cytocharasin B, but was inhibited by N-acetyl-leucyl-leucyl-norleucinal, the self-aggregated abnormal protein in the lumen of ER is assumed to be degraded by an unknown protease system other than proteasome, lysosome or autophagy [11].

Anatomical context of Allnal

• Here we describe a Chinese hamster ovary cell line that was selected for resistance to a synthetic tripeptide, N-acetyl-leucyl-leucyl-norleucinal (ALLN) [12].
• In the current studies we have explored oleate-stimulation of apoB secretion by using calpain inhibitor I, N-acetyl-leucyl-leucyl-norleucinal (ALLN), a compound that inhibits the intracellular degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and the T cell receptor alpha subunit [13].
• We observed that N-acetyl-leucyl-leucyl-norleucinal (ALLN), a synthetic aldehydic tripeptide that inhibits proteasomes, markedly induced Hsp70 levels (up to 30-fold above base line in HepG2 cells and human endothelial cells) [14].
• Although expression of MTP in cells allowed apoB to completely enter the endoplasmic reticulum, it was degraded by a proteolytic process that was inhibited by dithiothreitol (1 mM) and chloroquine (100 microM), but resistant to N-acetyl-leucyl-leucyl-norleucinal [15].
• The cysteine protease inhibitors leupeptin and N-acetyl-leucyl-leucyl-norleucinal (CI; preferential inhibitor of micromolar calpain but also inhibits millimolar calpain) at 10(-6) M considerably enhanced neurite outgrowth induced by serum deprivation, but could not induce neuritogenesis in the presence of serum [16].

Associations of Allnal with other chemical compounds

• The degradation of c-Fos preceded caspase-3 activation and apoptotic nuclear chromatin condensation and was inhibited by the proteasome inhibitors MG132, N-acetyl-leucyl-leucyl-norleucinal, and lactacystin [17].
• Indeed, treatment with three distinct calpain inhibitors (N-Ac-Leu-Leu-norleucinal, calpeptin, and ethyl(+)-(2S,3S)-3-[(S)-3-methyl-1-(3-methylbutylcarbamoyl)butyl-carbamoyl]-2-ox-iranecarboxylate) inhibited cell spreading induced by glucose and KCl, whereas cell attachment was not significantly modified [18].
• Of 14 protease inhibitor species examined, only a leupeptin analogue, Ac-Leu-Leu-Nle-al was stimulatory for neurite outgrowth in the presence of nerve growth factor [19].
• Synergistic induction of apoptosis of rheumatoid arthritis synovial cells by H(2)O(2) and N-acetyl-leucyl-leucyl-norleucinal [20].
• The downregulation of eNOS by nLDL was abrogated by cycloheximide, an inhibitor of protein synthesis, and by N-acetyl-leucyl-leucyl-norleucinal, a protease inhibitor that reduces the catabolism of sterol regulatory element binding proteins [21].

Gene context of Allnal

• Treatment with LMB results in dramatic retention of nuclear beta-catenin in normal epithelial cells transfected with LEF-1, and this effect is intensified by treatment of N-Acetyl-leucyl-leucyl-norleucinal together with LMB [22].
• The cysteine protease inhibitor N-acetyl-leucyl-leucyl-norleucinal, which inhibits SREBP degradation, enhanced the effect of SREBP-1a on the regulation of the rat HDL receptor SR-BI gene [23].
• Unexpectedly, however, like TNF-induced activation, H2O2-induced NF-kappaB activation was blocked by the calpain inhibitor N-Ac-Leu-Leu-norleucinal, suggesting that a proteosomal pathway was involved [24].
• The calpain inhibitors N-acetyl-leucyl-leucyl-norleucinal (ALLN) and N-acetyl-leucyl-leucyl-methional (ALLM) inhibited EPO-R degradation profoundly [25].
• The pulse-chase study showed that addition of N-acetyl leucyl leucyl norleucinal to the medium induced a decrease in newly synthesized apoB in the cell lysate in response to IL-1beta (P < 0.05) or IL-6 (not to a significant extent) compared with control [26].

References