|Description:||1. Lactacystin induces cell death and α-synuclein-positive inclusions in cytoplasm. |
2. Lactacystin has diversified killing effects on gastric cancer cells, the mechanism may be related to induce the apoptosis by downregulation of nuclear factor kappa B viability.
3. Lactacystin is a selective UPS inhibitor recently used to destroy dopamine (DA) neurons in animal models of Parkinson's disease (PD); marked differences in the rotational response to apomorphine and l-DOPA suggest different mechanisms of neurodegeneration evoked by Lactacystin and 6-OHDA.
|Targets:||GABA Receptor | HDAC | NF-kB | p65 | Caspase|
|Source:||From Streptomyces sp.|
|Solvent:||DMSO, Pyridine, Methanol, Ethanol, etc.|
|Storage:||Providing storage is as stated on the product vial and the vial is kept tightly sealed, the product can be stored for up to 24 months(2-8C).
Wherever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20C. Generally, these will be useable for up to two weeks. Before use, and prior to opening the vial we recommend that you allow your product to equilibrate to room temperature for at least 1 hour.
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|After receiving:||The packaging of the product may have turned upside down during transportation, resulting in the natural compounds adhering to the neck or cap of the vial. take the vial out of its packaging and gently shake to let the compounds fall to the bottom of the vial. for liquid products, centrifuge at 200-500 RPM to gather the liquid at the bottom of the vial. try to avoid loss or contamination during handling.|
|1 mg||5 mg||10 mg||20 mg||25 mg|
|1 mM||2.6565 mL||13.2827 mL||26.5654 mL||53.1307 mL||66.4134 mL|
|5 mM||0.5313 mL||2.6565 mL||5.3131 mL||10.6261 mL||13.2827 mL|
|10 mM||0.2657 mL||1.3283 mL||2.6565 mL||5.3131 mL||6.6413 mL|
|50 mM||0.0531 mL||0.2657 mL||0.5313 mL||1.0626 mL||1.3283 mL|
|100 mM||0.0266 mL||0.1328 mL||0.2657 mL||0.5313 mL||0.6641 mL|
Behav Brain Res. 2015 Apr 15;283:203-14.
|Decreased behavioral response to intranigrally administered GABAA agonist muscimol in the lactacystin model of Parkinson's disease may result from partial lesion of nigral non-dopamine neurons: comparison to the classical neurotoxin 6-OHDA.[Pubmed: 25655509]|
|Lactacystin is a selective UPS inhibitor recently used to destroy dopamine (DA) neurons in animal models of Parkinson's disease (PD). We found that both Lactacystin and 6-OHDA induced a strong decrease in DA level in the lesioned striatum and SN but only Lactacystin slightly reduced GABA levels in the SN. A stereological analysis showed that both neurotoxins highly decreased the number of DA neurons in the SN, while only Lactacystin moderately reduced the number of non-DA ones. Finally, in the Lactacystin group, the number of contralateral rotations after intranigrally administrated muscimol was decreased in contrast to the increased response in the 6-OHDA model. Our study proves that, although Lactacystin is not a fully selective to DA neurons, these neurons are much more vulnerable to its toxicity. Partial lesion of nigral non-DA neurons in this model may explain the decreased behavioral response to the GABAA agonist muscimol.|
Behav Brain Res. 2014 Mar 15;261:79-88.
|Chronic L-DOPA treatment attenuates behavioral and biochemical deficits induced by unilateral lactacystin administration into the rat substantia nigra.[Pubmed: 24361083]|
|The aim of the study was to determine whether the dopamine (DA) precursor l-DOPA attenuates parkinsonian-like symptoms produced by the ubiquitin-proteasome system inhibitor Lactacystin. Wistar rats were injected unilaterally with Lactacystin (2.5 μg/2 μl) or 6-OHDA (8 μg/2 μl) into the substantia nigra (SN) pars compacta. Four weeks after the lesion, the animals were treated chronically with l-DOPA (25 or 50 mg/kg) for two weeks. During l-DOPA treatment, the Lactacystin-treated rats were tested for catalepsy and forelimb asymmetry. However, the Lactacystin group did not respond to apomorphine or acute l-DOPA administration in the rotational test. Repeated l-DOPA treatment produced contralateral rotations in both PD models.Our study confirms the usefulness of the Lactacystin lesion as a model of PD. However, marked differences in the rotational response to apomorphine and l-DOPA suggest different mechanisms of neurodegeneration evoked by Lactacystin and 6-OHDA.|
Br J Pharmacol. 2015 Aug;172(16):4200-15.
|Neurorestoration induced by the HDAC inhibitor sodium valproate in the lactacystin model of Parkinson's is associated with histone acetylation and up-regulation of neurotrophic factors.[Pubmed: 26040297]|
|A known histone deacetylase inhibitor (HDACI), utilizing a delayed-start study design in the Lactacystin rat model of PD. EXPERIMENTAL APPROACH: The irreversible proteasome inhibitor Lactacystin was unilaterally injected into the substantia nigra of Sprague-Dawley rats that subsequently received valproate for 28 days starting 7 days after Lactacystin lesioning. Longitudinal motor behavioural testing, structural MRI and post-mortem assessment of nigrostriatal integrity were used to track changes in this model of PD and quantify neuroprotection/restoration. Subsequent cellular and molecular analyses were performed to elucidate the mechanisms underlying valproate's effects. KEY RESULTS: Despite producing a distinct pattern of structural re-modelling in the healthy and Lactacystin-lesioned brain, delayed-start valproate administration induced dose-dependent neuroprotection/restoration against Lactacystin neurotoxicity, characterized by motor deficit alleviation, attenuation of morphological brain changes and restoration of dopaminergic neurons in the substantia nigra. Molecular analyses revealed that valproate alleviated Lactacystin-induced histone hypoacetylation and induced up-regulation of brain neurotrophic/neuroprotective factors.|
Tumour Biol. 2015 May;36(5):3465-70.
|Investigation the mechanism of the apoptosis induced by lactacystin in gastric cancer cells.[Pubmed: 25541208]|
|The study aims to investigate the relationship between nuclear factor (nuclear factor kappa B (NF-κB)) viability and Lactacystin-mediated cell apoptosis in gastric cancer cells. Two gastric cancer cell lines (MKN28 and SGC7901) were treated with Lactacystin-a proteasome inhibitor for 24 h. Lactacystin reduced DNA binding viability of NF-κB (t = 3.0,P = 0.013) and the NF-κB viability (compared to the 5, 10 μmol/L MKN28 cell (p53 mutant) line, P < 0.001) and the expression of p65 NF-κB nuclear protein decreased parallelled to concentrations of Lactacystin in MKN28 cell line, while without obvious effects on NF-κB viability in SGC7901 cell line (P = 0.381), while the viability of caspase-3 increased also along with the raising of Lactacystin concentrations (compared to control, 5 μmol/L: SGC7901 cell line P = 0.029, MKN28 cell line P < 0.001; 10 μmol/L: SGC7901 cell line, P < 0.001, MKN28 cell line, P < 0.001). It was concluded that Lactacystin had diversified killing effects on gastric cancer cells.|
Neurosci Lett. 2014 Jul 11;575:25-30.
|Differential protein profile of PC12 cells exposed to proteasomal inhibitor lactacystin.[Pubmed: 24858133]|
|PC12 cells were treated with 10μM Lactacystin, a 20S proteasome inhibitor, for 24h. Lactacystin induced cell death and α-synuclein-positive inclusions in cytoplasm. Proteomic study identified 6 differentially expressed proteins between Lactacystin-treated and control cells in this study. Four proteins (heat shock 70kDa protein 8, 78kDa glucose-regulated protein, serine proteinase inhibitor clade B member 6 and aldehyde reductase) were increased and 2 proteins (peripherin and tyrosine hydroxylase) were decreased following proteasomal inhibition. The results revealed that PC12 cells treated with 10μM Lactacystin for 24h could be used as a cellular model of PD.|