Alteration of endocannabinoid system in human gliomas

J Neurochem. 2012 Mar;120(5):842-9. doi: 10.1111/j.1471-4159.2011.07625.x. Epub 2012 Jan 23.

Abstract

Endocannabinoids are neuromodulatory lipids that mediate the central and peripheral neural functions. Endocannabinoids have demonstrated their anti-proliferative, anti-angiogenic and pro-apoptotic properties in a series of studies. In the present study, we investigated the levels of two major endocannabinoids, anandamide and 2-arachidonylglycerol (2-AG), and their receptors, CB1 and CB2, in human low grade glioma (WHO grade I-II) tissues, high grade glioma (WHO grade III-IV) tissues, and non-tumor brain tissue controls. We also measured the expressions and activities of the enzymes responsible for anandamide and 2-AG biosynthesis and degradation, that is, N-acylphosphatidylethanolamine-hydrolysing phospholipase D (NAPE-PLD), fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MGL), and diacylglycerol lipase-alpha (DGL), in the same samples. Liquid chromatography-mass spectometry analysis showed that the levels of anandamide decreased, whereas the levels of 2-AG increased in glioma tissues, comparing to the non-tumor controls. The expression levels and activities of NAPE-PLD, FAAH and MGL also decreased in glioma tissues. Furthermore, quantitative-PCR analysis and western-blot analysis revealed that the expression levels of cananbinoid receptors, CB1 and CB2, were elevated in human glioma tissues. The changes of anandamide and 2-AG contents in different stages of gliomas may qualify them as the potential endogenous biomarkers for glial tumor malignancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Arachidonic Acids / metabolism
  • Brain / metabolism*
  • Brain Neoplasms / pathology*
  • Brain Neoplasms / physiopathology
  • Cannabinoid Receptor Modulators / metabolism*
  • Down-Regulation / physiology*
  • Endocannabinoids*
  • Female
  • Glioma / pathology*
  • Glioma / physiopathology
  • Glycerides / metabolism
  • Humans
  • Male
  • Middle Aged
  • Polyunsaturated Alkamides / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Cannabinoid / genetics
  • Receptors, Cannabinoid / metabolism*
  • Tritium / metabolism
  • Young Adult

Substances

  • Arachidonic Acids
  • Cannabinoid Receptor Modulators
  • Endocannabinoids
  • Glycerides
  • Polyunsaturated Alkamides
  • RNA, Messenger
  • Receptors, Cannabinoid
  • Tritium
  • glyceryl 2-arachidonate
  • anandamide