Disease relevance of Ac-Leu-Leu-Met-H

• Calpain inhibitor II induces caspase-dependent apoptosis in human acute lymphoblastic leukemia and non-Hodgkin's lymphoma cells as well as some solid tumor cells [1].
• Spectrin breakdown products mediated by calpain 1 activation were detectable in both hemispheres 24 h after traumatic brain injury and were substantially reduced in animals treated with calpain inhibitor 2 both ipsilaterally and contralaterally to the site of injury [2].
• Results indicated that Calpain Inhibitor II treatment after SAH significantly improved (a) beam balance time (day 1, p < 0.05), but not beam balance score, (b) latency to traverse the beam on days 1-4 (day 1-3, p < 0.001; day 4, p < 0.01), and (c) loss in body weight on days 4-5 (p < 0.05) [3].
• We examined the therapeutic potential of calpain inhibitor 2, compared with that of moderate hypothermia in traumatic brain injury produced by weight drop in rats [4].

High impact information on Ac-Leu-Leu-Met-H

• Calpain inhibitors N-acetyl-leu-leu-norleucinal (ALLN) and N-acetyl-leu-leu-methioninal (ALLM) reduced calpain activity and expression and restored SEC cell shape and actin morphology [5].
• Cysteine protease inhibitors E64 and calpain inhibitor II, which do not block NF-kappaB activation, do not induce HSF DNA binding activity [6].
• The calcium ionophore A23187 destabilized YY1 in cultured myoblasts, and the decrease in YY1 protein levels could be prevented by calpain inhibitor II and calpeptin [7].
• Calpain inhibitor II similarly blocked formation of the calpain-mediated 40-kDa fragment both in situ and in vitro [8].
• In addition to preventing the reduction in IRS-1, treatment of cells with calpain inhibitor II prevents apoptosis in response to thapsigargin [9].

Biological context of Ac-Leu-Leu-Met-H

• Calpain inhibitor II and the pan-caspase inhibitor Z-D-DCB each inhibited their respective protease-specific processing of alpha-spectrin and attenuated endonuclease DNA fragmentation and cell death [10].
• Calpain inhibitor II and MG2M, which is a structural analogue of MG115, had no effect on the cell cycle [11].
• Calpain inhibitor II inhibited calpain-specific processing of alpha-spectrin and significantly reduced cell death [12].
• Down-regulation of PKCs in the membrane fraction was partially blocked by calpain inhibitor II [13].

Anatomical context of Ac-Leu-Leu-Met-H

• Calpain inhibitor 2 prevents axonal degeneration of opossum optic nerve fibers [14].
• Calpain inhibitor 2, administered 10 min after injury via continuous arterial infusion into the right external carotid artery for 24 h, significantly reduced neurofilament 200 losses to 17% and 3% relative to naive neurofilament 200 protein levels in the ipsilateral and contralateral cortices, respectively [2].
• Accordingly, we investigated the effects of lactacystin, a proteasome inhibitor, and calpain inhibitor-II (CI-II) on L8 muscle cell differentiation and assessed concentrations of proteasomal and calpain subunit mRNAs during differentiation [15].
• We show that the extracellular application of two newly developed, highly potent calpain inhibitors, N-acetyl-Leu-Leu-norleucinal and N-acetyl-Leu-Leu-methioninal, block LTP in both the Schaffer collateral-CA1 synaptic zone of the rat hippocampal slice and in perforant path-stimulated dentate granule cells in the intact hippocampus [16].

Associations of Ac-Leu-Leu-Met-H with other chemical compounds

• The migration of SCC cells through a gelatin-coated membrane was enhanced with tumor necrosis factor alpha (TNF alpha), which was strongly inhibited by a peptide aldehyde, N-acetyl-Leu-Leu-norleucinal (ALLN), but not by its structurally related compound, N-acetyl-Leu-Leu-methioninal (ALLM) [17].
• Simultaneous injection of 2 nmol of a calpain inhibitor (calpain inhibitor II) significantly reduced the number of TUNEL-positive cells in the inner retina at 18 h after NMDA injection and preserved RGC-like cells counted at 7 days after injection [18].
• Our results indicate that calpain inhibitor I, calpain inhibitor II, and leupeptin all provided significant protection of SGNs against neurotrophin-withdrawal and hypoxia-induced apoptosis [19].
• Furthermore, it was shown that, in methylmercury-exposed cells, alpha-fodrin and tau, calpain substrates, were cleaved to the fragments that disappeared by treatment with the calpain inhibitor II [20].

Gene context of Ac-Leu-Leu-Met-H

• When m-calpain activity and myoblast fusion were prevented by addition of antibodies to m-calpain or calpain inhibitor II, the fibronectin concentration was higher since it was increased by approximately 67 and approximately 71%, respectively [21].
• Calpain inhibitor II (N-acetyl-Leu-Leu-methionyl) provided protection only with a narrow dose range, whereas carbobenzoxy-Asp-CH2-OC(O)-2,6-dichlorobenzene (Z-D-DCB; pan-caspase inhibitor) and MK-801 (N-methyl-D-aspartate receptor antagonist) were potently effective across a wider dose range [22].
• Calpain inhibitors E64d (100 microM) and calpain inhibitor II (1 mM) were ineffective in preventing opacity formation caused by DCVC [23].
• Staurosporine-induced loss of neuronal particles was blocked by nonselective caspase inhibition (z-VAD-fmk) and by calpain inhibition (calpain inhibitor II [ALLM]) [24].
• Moreover, protease inhibitors fail to abrogate CD95 ligand-induced apoptosis even though DNA fragmentation is attenuated by calpain inhibitor II and TPCK [25].

References