Canna~Fangled Abstracts

Virodhamine, an endocannabinoid, induces megakaryocyte differentiation by regulating MAPK activity and function of mitochondria

By July 22, 2020 July 23rd, 2020 No Comments

doi: 10.1002/jcp.29949. Online ahead of print.



Endocannabinoids are well-known regulators of neurotransmission by activating the cannabinoid (CB) receptors. Endocannabinoids are being used extensively for the treatment of various neurological disorders such as Alzheimer’s and Parkinson’s diseases. Although endocannabinoids are well studied in cell survival, proliferation, and differentiation in various neurological disorders and several cancers, the functional role in the regulation of blood cell development is less examined. In the present study, virodhamine, which is an agonist of CB receptor-2, was used to examine its effect on megakaryocytic development from a megakaryoblastic cell. We observed that virodhamine increases cell adherence, cell size, and cytoplasmic protrusions. Interestingly, we have also observed large nucleus and increased expression of megakaryocytic marker (CD61), which are the typical hallmarks of megakaryocytic differentiation. Furthermore, the increased expression of CB2 receptor was noticed in virodhamine-induced megakaryocytic cells. The effect of virodhamine on megakaryocytic differentiation could be mediated through CB2 receptor. Therefore, we have studied virodhamine induced molecular regulation of megakaryocytic differentiation; mitogen-activated protein kinase (MAPK) activity, mitochondrial function, and reactive oxygen species (ROS) production were majorly affected. The altered mitochondrial functions and ROS production is the crucial event associated with megakaryocytic differentiation and maturation. In the present study, we report that virodhamine induces megakaryocytic differentiation by triggering MAPK signaling and ROS production either through MAPK effects on ROS-generating enzymes or by the target vanilloid receptor 1-mediated regulation of mitochondrial function.


Keywords: MAPK, ROS, endocannabinoid, megakaryocyte, mitochondria, virodhamine




    1. Alberich Jordà, M., Rayman, N., Tas, M., Verbakel, S. E., Battista, N., van Lom, K., … Delwel, R. (2004). The peripheral cannabinoid receptor Cb2, frequently expressed on AML blasts, either induces a neutrophilic differentiation block or confers abnormal migration properties in a ligand-dependent manner. Blood, 104(2), 526-534.
    1. Assinger, A. (2014). Platelets and infection-an emerging role of platelets in viral infection. Frontiers in Immunology, 5, 649.
    1. Athanasiou, A., Clarke, A. B., Turner, A. E., Kumaran, N. M., Vakilpour, S., Smith, P. A., … Bates, T. E. (2007). Cannabinoid receptor agonists are mitochondrial inhibitors: A unified hypothesis of how cannabinoids modulate mitochondrial function and induce cell death. Biochemical and Biophysical Research Communications, 364(1), 131-137.
    1. Berdyshev, E. V., Schimd, P. C., Krebsbach, R. J., & Schmid, H. H. (2001). Activation of PAF receptors results in enhanced synthesis of 2-arachidonoylglycerol (2-AG) in immune cells. FASEB Journal, 15, 2171-2178.
    1. Bisogno, T., Maurelli, S., Melck, D., De Petrocellis, L., & Di Marzo, V. (1997). Biosynthesis, uptake, and degradation of anandamide and palmitoylethanolamide in leukocytes. Journal of Biological Chemistry, 272, 3315-3323.

Leave a Reply

en English