Inhibition of Serine Palmitoyltransferase by Myriocin, a Natural Mycotoxin, Causes Induction of C-Myc in Mouse Liver

Details

• Personal Author:
  He Q ; Johnson VJ ; Osuchowski MF ; Sharma RP
• Description:
  Myriocin, a fungal metabolite isolated from Myriococcum albomyces, Isaria sinclairi, and Mycelia sterilia, is a potent inhibitor of serine palmitoyltransferase (SPT), a key enzyme in de novo synthesis of sphingolipids. To evaluate the biological effects of myriocin in vivo, we investigated the levels of free sphingoid bases and expression of selected genes regulating cell growth in mouse liver. Male Balb/c mice, weighing 22 g were injected intraperitoneally with myriocin at 0, 0.1, 0.3, and 1.0 mg kg-1 body weight daily for 5 days. Animals were euthanized 24 hours after the last treatment. Levels of plasma alanine aminotransferase and aspartate aminotransferase were not significantly altered by the treatment. A dose-dependent decrease in free sphinganine but not sphingosine was detected by high performance liquid chromatography in both liver and kidney. The decrease of free sphinganine paralleled the decrease in SPT activity. Reverse transcriptase polymerase chain reaction analysis on liver mRNA revealed an increase in expression of c- myc, but no changes in tumor necrosis factor a, transforming growth factor ß, and hepatocyte growth factor. Results showed that myriocin blocked de novo synthesis of sphingolipids in vivo by SPT inhibition and induced c- myc expression in liver. [Description provided by NIOSH]
• Subjects:
  Energy Metabolism Fungi Fungicide, Industrial Laboratories Microbiology Occupational Health Safety
• Keywords:
  Fungicides In-vivo-study Laboratory-animals Liver Liver-cells Metabolism Metabolites Microorganisms
• ISSN:
  0301-486X
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  339-347
• Volume:
  157
• Issue:
  3
• NIOSHTIC Number:
  nn:20025273
• Citation:
  Mycopathologia 2004 Apr; 157(3):339-347
• Federal Fiscal Year:
  2004
• Peer Reviewed:
  True
• Source Full Name:
  Mycopathologia
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:89ab6ef4ee8c519cc03f4bfb3230235f6a1d9dc391b26ec3c158dbeaca92ca642d6bbf81343546865926676ecd915a44a13a4cb31bc4187b3494445094dc7b07
• Download URL:
  https://stacks.cdc.gov/view/cdc/196721/cdc_196721_DS1.pdf
• File Type:
  [PDF - 281.80 KB ]