• 미생물과산업
• /
• 제13권1호
• /
• pp.10-13
• /
• 1987

L-Azetidine-2-carboxylic acid(A-2-C) is a four-membered cyclic imino acid which was first discovered from Convalaria majalis and Polygonatum officinalis in 1955(1,2). The imino acid A-2-C has been identified in at least 16 species of plants (3) (mostly the families Liliaceae, Agavaceae and Amaryllidaceae); in two marine sponges (Haliclona sp. and Chalinospilla sp.) (4); in the red algae (Lophocladia lamenandi) (5); in the sugar beet Beta vulgaris (6) ; and the microorganism Actinoplanes ferrugineus (7).

• Bulletin of the Korean Chemical Society
• /
• 제29권10호
• /
• pp.2033-2035
• /
• 2008

• BMB Reports
• /
• 제51권11호
• /
• pp.590-595
• /
• 2018

Parkinson's disease (PD) is a common chronic neurodegenerative disease mainly caused by the death of dopaminergic neurons. However, no complete pharmacotherapeutic approaches are currently available for PD therapies. 1-methyl-4-phenylpyridinium $(MPP^+)$-induced SH-SY5Y neurotoxicity has been broadly utilized to create cellular models and study the mechanisms and critical aspects of PD. In the present study, we examined the role of a novel azetidine derivative, 3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride (KHG26792), against $MPP^+$-induced neurotoxicity in SH-SY5Y cells. Treatment of KHG26792 significantly attenuated $MPP^+$-induced changes in the protein levels of Bcl-2 and Bax together with efficient suppression of $MPP^+$-induced activation of caspase-3 activity. KHG26792 also attenuated mitochondrial potential and levels of ROS, $Ca^{2+}$, and ATP in $MPP^+$-treated SH-SY5Y cells. Additionally, KHG26792 inhibited the induced production of nitric oxide and malondialdehyde. Moreover, the protective effect of KHG26792 is mediated through regulation of glutathione peroxidase and GDNF levels. Our results suggest a possibility that KHG26792 treatment significantly protects against $MPP^+$-induced neurotoxicity in SH-SY5Y cells and KHG26792 may be a valuable therapeutic agent for the treatment of PD induced by an environmental toxin.

• BMB Reports
• /
• 제49권12호
• /
• pp.687-692
• /
• 2016

We recently reported the anti-inflammatory effects of 3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride (KHG26792) on the ATP-induced activation of the NFAT and MAPK pathways through the P2X7 receptor in microglia. To further investigate the underlying mechanism of KHG26792, we studied its protective effects on hypoxia-induced toxicity in microglia. The administration of KHG26792 significantly reduced the hypoxia-induced expression and activity of caspase-3 in BV-2 microglial cells. KHG26792 also reduced hypoxia-induced inducible nitric oxide synthase protein expression, which correlated with reduced nitric oxide accumulation. In addition, KHG26792 attenuated hypoxia-induced protein nitration, reactive oxygen species production, and NADPH oxidase activity. These effects were accompanied by the suppression of hypoxia-induced protein expression of hypoxia-inducible factor 1-alpha and NADPH oxidase-2. Although the clinical relevance of our findings remains to be determined, these data results suggest that KHG26792 prevents hypoxia-induced toxicity by suppressing microglial activation.

• 한국작물학회:학술대회논문집
• /
• 한국작물학회 2001년도 춘계 학술대회지
• /
• pp.258-259
• /
• 2001

• 대한화학회지
• /
• 제52권6호
• /
• pp.649-656
• /
• 2008

• BMB Reports
• /
• 제31권2호
• /
• pp.201-208
• /
• 1998

Amino acid analogs, like other inducers of stress response, induce the synthesis of stress proteins in mammalian cells. In this study, Drosophila Kc cells, in which translation is tightly controlled during stress response, was treated with proline analogs, L-azetidine-2-carboxylic acid (AzC) and 3,4-dehydro-L-proline (dh-P). Kc cells exposed to AzC or dh-P induced the synthesis of several proteins which had the same molecular weights as known heat shock proteins. However, in Kc cells, normal protein synthesis still continued in the presence of amino acids analogs unlike in heat-shocked cells. For the induction of stress response, the incorporation of dh-P into the protein was not essential, but the incorporation of AzC was. The stress protein synthesis was regulated mainly at the transcriptional level by AzC, whereas it was regulated by dh-P at the transcription level and possibly posttranscription level. During recovery, the stress protein synthesis stopped sooner in analog-treated cells than in heat-shocked cells even though the accumulated amount of Hsp70 was much less in proline analogstreated cells. It could be concluded that the proline analogs, AzC and dh-P, induced stress response through a different mechanism from heat shock.

• BMB Reports
• /
• 제50권12호
• /
• pp.634-639
• /
• 2017

We aimed to assess the anti-inflammatory and antioxidative properties of KHG26792, a novel azetidine derivative, in amyloid ${\beta}$ ($A{\beta}$)-treated primary microglial cells. KHG26792 attenuated the $A{\beta}-induced$ production of inflammatory mediators such as IL-6, $IL-1{\beta}$, $TNF-{\alpha}$, and nitric oxide. The levels of protein oxidation, lipid peroxidation, ROS, and NADHP oxidase enhanced by $A{\beta}$ were also downregulated by KHG26792 treatment. The effects of KHG26792 against the $A{\beta}-induced$ increases in inflammatory cytokine levels and oxidative stress were achieved by increasing the phosphorylation of $Akt/GSK-3{\beta}$ signaling and by decreasing the $A{\beta}-induced$ translocation of $NF-{\kappa}B$. Our results provide novel insights into the use of KHG26792 as a potential agent against $A{\beta}$ toxicity, including its role in the reduction of inflammation and oxidative stress. Nevertheless, further investigations of cellular signaling are required to clarify the in vivo effects of KHG26792 against $A{\beta}-induced$ toxicity.

• 한국미생물생명공학회:학술대회논문집
• /
• 한국미생물생명공학회 1986년도 추계학술대회
• /
• pp.505.2-506
• /
• 1986

L-Azetidine-2-carboxylic acid (A-2-C), a four-membered cyclic imino acid has been identified in certain plants, and the microorganism Actinoplanes ferrugineus. The imino acid A-2-C has a physiological significance as an antgaonist of proline during peptide synthesis. The biosynthetic mechanism for the formation of A-2-C has not been studied in any detail. By using various amino acids such as methionine and S-adenosyl-L-methionine labeled with deuterium or carbon-14, the details of the biosynthetic pathway and a possible mechanism for the formation of L-A-2-C in .4. ferrugineus have been unravelled, Both in vivo and in vitro experimental results suggest the biosynthesis of L-A-2-C is mediated by a confactor containing a carbonyl group, probably pyridoxal Phosphate. S-Adenosyl-L-methionine, which seems to be the direct biosynthetic substrate, has undergone a f-displacement by an ${\alpha}$-amino group of the amino acid portion of the substrate S-adenosyl-L-methionine potentially via a vinylglycine intermediate. The overall stereochemical events at the ${\beta}$-carbon of the substrate have been shown to inversion of configuration. The overall stereochemical events at the -position of the sub- strate have also been shown to occur with inversion of configuration. The ${\beta}$, ${\gamma}$-elimination reaction of the substrate seems to follow a cisoidal-type mechanism and the addition portion of the reaction a transoidal-type mechanism . The assignment of the proton NMR of A-2-C has been deduced by apply- ing NOE difference experiments, Gd(III) line-broadening experiments and 2D-NOESY experiments of regio-and stereospecificially deuterated A-2-C's.

• Journal of Plant Biotechnology
• /
• 제5권1호
• /
• pp.43-49
• /
• 2003

Resistant cell lines to azetidine-2-carboxylic acid (AZCA) were selected through rice embryo culture after mutagenic treatment of callus irradiated with 30,50,70,90 and 120 Gy. The optimum AZCA concentration for the selection of resistant cell lines was 3 or 4 mM AZCA considering $LD_{50}$ and the fresh weight of callus. Survival rate of the AZCA resistant callus showed remarkable increase in the callus irradiated with 50 and 70 Gy. Regeneration rate of the AZCA resistant callus was much lower on the whole. Ninety and 120 Gy increased the regeneration rate for calli selected from 3 and 4 mM AZCA, respectively. Based on fresh weight, survival rate and regeneration for selection of the AZCA resistant cell line, 50-90 Gy was considered as the optimum range of gamma irradiation. Irradiated calli selected from AZCA were more tolerant to NaCl than those from non-irradiated calli. It suggests that elevated resistance to osmotic stress resulted from mutagenic treatment. The level of free proline content in the AZCA resistant cell line was increased up to 3.5 times compared with that in the control. Proline content in the regenerant derived from the AZCA resistant cell line also increased to 1.7 times that from the control plants regenerated from callus grown in AZCA free medium. Selection of proline overproducing cell lines by in vitro mutagenesis was successful and seems to be useful for improvement of stress tolerance in this crop.