The endocannabinoid 2-arachidonoylglicerol decreases calcium induced cytochrome c release from liver mitochondria |
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Authors: | Patrizia Zaccagnino Susanna D’Oria Luigi Luciano Romano Almerinda Di Venere Anna Maria Sardanelli Michele Lorusso |
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Institution: | Department of Basic Medical Sciences, University of Bari, Policlinico, Piazza G. Cesare, 70124 Bari, Italy. |
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Abstract: | 2-Arachidonoylglicerol (2-AG) is an endocannabinoid that mimics the pharmacological effects of Δ9 tetrahydrocannabinol, the psychoactive component of the plant Cannabis sativa. It is present in many mammalian tissues, such as brain, liver, spleen, heart and kidney, where it exerts different biological
effects either receptor mediated or independently of receptor activation. This work analyzes the effects of 2-AG on liver
mitochondrial functions. It is shown that 2-AG causes a relevant decrease of calcium induced cyclosporine A sensitive cytochrome
c release from mitochondria, a process representing an early event of the apoptotic program. Cyclosporin sensitive matrix
swelling and ROS production measured under the same conditions are, on the contrary, almost unaffected or even enhanced, respectively,
by 2-AG. Furthemore, 2-AG is found to stimulate resting state succinate oxidase activity and to inhibit oligomycin sensitive
FoF1 ATP synthase activity. All these effects are apparently associated with 2-AG dependent alteration in the fluidity of the
mitochondrial membranes, which was measured as generalized polarization of laurdan fluorescence. |
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