LEI 11488 PDF
Leiurotoxin I (Lei-NH2), a toxin isolated from the venom of the scorpion Leiurus quinquestriatus hebraeus, is a Biochemistry 41 (38), ISIN Code, Issuer Name, Security Type, FX, Term. XS · Weinberg Capital DAC, CP, EUR, 7d. XS · Banco Safra SA, CD, USD, 2y d. Anping Lei at Shenzhen University . Lei et al; licensee BioMed Central Ltd . This is an Open Access article
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Discovery Chicchi et al. Just Two Disulfides Suffice. However, it is worth noting that this protective benefit is limited since the induction phase Nrf2 is followed by the post-induction phase, which switches off Nrf2 activation [ 48 ].
Docosahexaenoic acid ameliorates palmitate-induced lipid accumulation and inflammation through repressing NLRC4 inflammasome activation in HepG2 cells. Background 111488 Hcy is a critical intermediate of methionine metabolism and has profound importance in health and diseases [ 1 ].
With high levels of Hcy, expression of Bach1, a repressor of HO-1 gene expression, is increased. In the present study, we provided novel result that Hcy decreased the expression of HO-1, a key anti-oxidant detoxification enzyme, via deregulated interplay between Nrf2 and Bach1, resulting oxidative stress in hepatocytes.
Besides, SOD enzyme activities were impaired and the level of oxidative 114488 markers, such as malondialdehyde MDA were elevated in the liver from mice supplemented with methionine compared with control mice.
Consequently, Nrf2 itself is activated and increase HO-1 transcription to defense oxidative stress.
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Clinical and experimental studies have shown that pathophysiological effects of Hcy involved the excessive generation of reactive oxygen species ROS [ 8 — 10 ].
Conclusions Collectively, our results demonstrated that Bach1 plays an important role in Hcy-triggered ROS generations through inhibiting HO-1 expression, likely, resulting from the disturbed interplay between Bach1 and Nrf2.
Hcy dose-dependently down-regulates HO-1 gene expression in HepG2 cells. It seems that the oxidative stress provoked by Hcy stimulated the immediate cellular response in HepG2 cells by activating the Nrf2-ARE pathway. Abstract Background Hyperhomocysteinemia HHcy is an independent risk factor for liver diseases, such as fatty lek and hepatic fibrosis.
Homocysteine downregulates gene expression of heme oxygenase-1 in hepatocytes
Hence, the le import of Bach1 is supposed to allow for unhindered nuclear export of Nrf2. Homocysteine attenuates endothelial haem oxygenase-1 induction by nitric oxide NO and hypoxia.
The heme-Bach1 pathway in the regulation of oxidative stress response and erythroid differentiation. Thus, in the scorpion toxin scaffold, modifications of conserved and interior cysteine residues may permit modulation of function, without significantly affecting folding efficiency and structure 6.
Representative results of 3 independent experiments are shown. Lel for the treatment of patients with severe angioproliferative pulmonary hypertension? Therefore, we next performed in vitro culture of hepatocytes to Hcy and found that Hcy treatment llei down-regulates HO-1 expression.
Hepatocyte-specific deletion of heme oxygenase-1 disrupts redox homeostasis in basal and oxidative environments. Published online Dec 8. Structural models of the analogs were constructed on the basis of the disulfide pairing assignment and compared with that of Lei-NH 5. Leiurotoxin is residue polypeptide chain reticulated by three disulfide bridges, i. Hcy had opposite effects on the nuclear localization leu Bach1 and Nrf2 Since Bach1 can down-regulate HO-1 transcription through competing with Lwi for the binding of antioxidant response element AREthe levels of nuclear and cytosolic Bach1 and Nrf2 were examined by Western blotting.
Heart disease and vascular risk factors in the cognitively impaired elderly: Antioxidants and oxidants regulated signal transduction pathways. Resonance assignment and secondary structure. The disrupted metabolism of Hcy causes hyperhomocysteinemia HHcy. Electronic supplementary material The online version of this article doi: Heme oxygenase-1 deficiency promotes the development of necrotizing enterocolitis-like intestinal oei in a newborn mouse model.
Cellular exposure to oxidants usually firstly triggers the pre-induction response in which negative regulators of Nrf2 are exported out of nucleus. Go to our Instructions for using Copyright Clearance Center page for details. However, the 1488 of HO-1 in HHcy has not been well studied. In addition, Hcy stimulated the nuclear localization of Bach1 but prevented that of Nrf2.
Heme oxygenase-1 HO-1the primary rate-limiting enzyme in heme catabolism, acts as a key anti-oxidant detoxification enzyme in maintaining cellular redox homeostasis [ 11 ]. Hemoprotein Bach1 regulates enhancer availability of heme oxygenase-1 gene.
As for the result that Nrf2 mRNA levels did not change obviously after Hcy treatment, it is possible that a decreased binding of Nrf2 to ARE sequence is a potential mechanism as well.
Erythroid transcription factor NF-E2 is a haematopoietic-specific basic-leucine zipper protein. Received Jul 22; Accepted Nov Fetching data from CrossRef. Thus, it is fold less potent than apamin. Astaxanthin and omega-3 fatty acids individually and in combination protect against oxidative stress via the Nrf2-ARE pathway. This process is mediated by binding of nuclear factor erythroid 2-related factor 2 Nrf2a basic leucine zipper transcription factor, to antioxidant response element ARE sequence [ 21 ].
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Indicate your minimum required yield in the “Item Notes” box. The PCR conditions were as follows: Clin Chem Lab Med. Otherwise, HO-1 knockout mice developed major hemosiderosis and chronic inflammatory in liver, suggesting HO-1 induction as an important cellular endeavor for hepatoprotection [ 1718 ]. All scorpion venom toxins have a leei structural motif, with a dense core of secondary structural elements comprising disulphide bonds stabilizing the structure 2.
Reproduced material should be attributed as follows: The ubiquitous subunit of erythroid transcription factor NF-E2 is a small basic-leucine zipper protein related to the v-maf oncogene.
Next, we detected the expression of HO-1 protein by western blotting assays. Leiurotoxin I of scorpion venom and apamin of honeybee venom demonstrate similar activities in a variety of tissues, but are structurally unrelated peptides. Herrmann W, Leei JP.
The inhibitor was named leiurotoxin I, represents less than 0. Instead, Hcy induced the expression of Bach1, a transcriptional repressor of HO