A novel neuronal cell protecting substance, halxazone, produced by Streptomyces halstedii.

  title={A novel neuronal cell protecting substance, halxazone, produced by Streptomyces halstedii.},
  author={Hironobu Katoh and Kazuo Shin‐ya and Kazuo Furihata and Keiko Furihata and Yoichi Hayakawa},
  journal={The Journal of antibiotics},
  volume={55 5},
Parkinson's disease (PD) is characterized by selective degeneration of dopaminergic neurons in the substantia nigra. Although the accurate etiology of Parkinson's disease is not clear, one of the hypothetical factors is oxidative stress. The excess administration of L-DOPA, which is an effective drug in PD therapy, results in the worsening of Parkinson's disease, by generating reactive oxygen species (ROS)1-3). Thus, the advance of PD may be expected to be overcome by substances which suppress… 
2 Citations
Apoptotic mechanisms involved in neurodegenerative diseases: experimental and therapeutic approaches.
It is postulated that multitargeting therapies comprising antioxidants, cell cycle inhibitors and modulating agents of COX-2 or c-JUN kinase pathways could be suitable strategies to prevent or delay the process of neuronal cell death in neurodegenerative disorders.


Induction of apoptosis in catecholaminergic PC12 cells by L-DOPA. Implications for the treatment of Parkinson's disease.
The finding that L-DOPA-induced cell death in vitro occurs via apoptosis explains the lack of evidence supporting its toxicity in vivo, since apoptotic neurons are rapidly phagocytosed in vivo without causing damage to surrounding tissue.
l‐DOPA Cytotoxicity to PC12 Cells in Culture Is via Its Autoxidation
The data suggest that toxicity of l‐DOPA is most likely due to the action of free radicals formed as a result of its autoxidation, and that patients on long‐term l-DOPA therapy are potentially at risk from the toxic intermediates formed as an result of it autoxidated.
Antioxidants protect against glutamate-induced cytotoxicity in a neuronal cell line.
Results indicate that oxidative stress due to loss of cellular levels of GSH is one mechanism whereby Glu/quisqualate exert cytotoxicity and suggest that centrally active antioxidants may reduce neuronal damage in pathologic conditions associated with excessive Glu release.
A new neuronal cell protecting substance, lavanduquinocin, produced by Streptomyces viridochromogenes.
A new neuronal cell protecting substance, lavanduquinocin was isolated from Streptomyces viridochromogenes 2942-SVS3 and protected neuronal hybridoma N18-RE-105 cells from L-glutamate toxicity with EC50 value 15.5 nm.
A neuronal cell protecting substance, 4-demethoxymichigazone, produced by Streptomyces halstedii.
The aqueous residue was extracted with EtOAc, and the organic layer was, after drying over Na2SO4, evaporated to give an oily residue.
Enhancing Effect of Manganese on L‐DOPA‐Induced Apoptosis in PC12 Cells
The data show that agents that induce oxidative stress‐mediated apoptosis in catecholaminergic cells may act synergistically, and an increase in autoxidation of L‐DOPA and of newly formed DA is suggested as a mechanism of manganese action.
Immature cortical neurons are uniquely sensitive to glutamate toxicity by inhibition of cystine uptake
  • T. Murphy, R. Schnaar, J. Coyle
  • Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 1990
It is demonstrated that primary cultures of rat cortical neurons, but not glia, also degenerate when exposed to culture medium with reduced cystine or containing competitive inhibitors of cyStine uptake, including glutamate.
[Mitomycin and a new phenoxazone pigment from Streptomyces michiganensis. Metabolic products of microorganisms (author's transl)].
In contrary to all known phenoxazones from micro-organisms the new compound lacks a 2-amino-function, but could be enhanced by optimizing the condtions of fermentation.
Structure and syntheses of texazone. 2-(N-methylamino)-3H-phenoxazin-3-one-8-carboxylic acid, an actinomycete metabolite.
Cultures of actinomycete strain WRAT-210 produced a dark red crystalline metabolite which was named texazone, and the structure was confirmed by chemical synthesis through oxidative dimerization of ethyl 3-amino-4-hydroxybenzoate with 2-(N-methylamino)phenol and subsequent hydrolysis of the resultant phenoxazinone ester.