Direct inhibition of the mitochondrial permeability transition pore: a possible mechanism responsible for anti-apoptotic effects of melatonin 1 SHAIDA A. ANDRABI * , IQBAL SAYEED † , DETLEF SIEMEN † , GERALD WOLF * and THOMAS F. W. HORN * ,2 * Institute for Medical Neurobiology and † Department of Neurology Otto-von-Guericke University, Magdeburg, Germany 2 Correspondence: Leipziger St. 44, Haus 36, Magdeburg, D-39120 Germany. E-mail: thomas.horn@medizin.uni-magdeburg.de <h3>SPECIFIC AIM</h3> We investigate whether the pineal hormone melatonin directly inhibits potentially proapoptotic mitochondrial permeability transition pore (mtPTP) activity at single-channel and cellular levels. We examined whether such mtPTP inhibition by melatonin leads to decreased NMDA receptor-induced increase in cytosolic calcium ([Ca 2+ ] c ). <h3>PRINCIPAL FINDINGS</h3> 1. Melatonin reduces sustained [Ca 2+ ] c increase in primary neuronal cultures exposed to NMDA Upon stimulation of striatal neurons with 200 µM NMDA, we observed a fast increase in the fluo-4 fluorescence from a baseline intensity of 103.4 ± 4.3 (average of single cell arbitrary intensity values ± SE, n =5 cultures) to 282.3 ± 22.5 immediately after exposure to NMDA (<h3>Fig. 1</h3> ). The increased fluorescence, indicating an increase in [Ca 2+ ] c , was still high (284.3±16.2) 18
/lp/fed-of-american-socs-for-experimental-biology/direct-inhibition-of-the-mitochondrial-permeability-transition-pore-a-YhSIWaltua