Biochemical and pharmacological evidence supports the hypothesis that the mechanism of action of mildronate [3-(2,2,2-trimethylhydrazinium)propionate dihydrate] is based on its regulatory effect on carnitine concentration. The present study demonstrates that carnitine acts as a neuroprotective agent both in optic nerve head and in retinal ganglion cell (RGC) by means of antioxidant and antiradical activities. In fact, carnitine normalized the increase in caspase-3, cellular apoptosis susceptibility protein (CAS) and inducible nitric oxide synthase (iNOS) expression by stabilizing mitochondrial membranes, as assessed by quantitative and qualitative analysis. This research shows that the neuroprotective effects of carnitine result, at least partially, from anti-neurodegenerative (anti-apoptotic) and anti-inflammatory mechanisms. It is suggested that the molecular conformation of carnitine can facilitate its easy binding to mitochondria, and regulate the expression of different signal molecules, hence maintaining normal cellular signaling and survival by modulating caspase-3 activity.

DEGENERATIVE EVENTS IN RETINA AND OPTIC NERVE INDUCED BY INHIBITION OF CARNITINE TRANSPORT / Pescosolido, Nicola; Pascarella, Antonia; Nebbioso, Marcella; Scarsella, Gianfranco. - In: JOURNAL OF BIOLOGICAL REGULATORS & HOMEOSTATIC AGENTS. - ISSN 0393-974X. - STAMPA. - 28:2(2014), pp. 263-270.

DEGENERATIVE EVENTS IN RETINA AND OPTIC NERVE INDUCED BY INHIBITION OF CARNITINE TRANSPORT

PESCOSOLIDO, Nicola;PASCARELLA, ANTONIA;NEBBIOSO, Marcella;SCARSELLA, Gianfranco
2014

Abstract

Biochemical and pharmacological evidence supports the hypothesis that the mechanism of action of mildronate [3-(2,2,2-trimethylhydrazinium)propionate dihydrate] is based on its regulatory effect on carnitine concentration. The present study demonstrates that carnitine acts as a neuroprotective agent both in optic nerve head and in retinal ganglion cell (RGC) by means of antioxidant and antiradical activities. In fact, carnitine normalized the increase in caspase-3, cellular apoptosis susceptibility protein (CAS) and inducible nitric oxide synthase (iNOS) expression by stabilizing mitochondrial membranes, as assessed by quantitative and qualitative analysis. This research shows that the neuroprotective effects of carnitine result, at least partially, from anti-neurodegenerative (anti-apoptotic) and anti-inflammatory mechanisms. It is suggested that the molecular conformation of carnitine can facilitate its easy binding to mitochondria, and regulate the expression of different signal molecules, hence maintaining normal cellular signaling and survival by modulating caspase-3 activity.
2014
antioxidant activity; carnitine; cytotoxicity; mildronate; neuroprotection; optic nerve; retina
01 Pubblicazione su rivista::01a Articolo in rivista
DEGENERATIVE EVENTS IN RETINA AND OPTIC NERVE INDUCED BY INHIBITION OF CARNITINE TRANSPORT / Pescosolido, Nicola; Pascarella, Antonia; Nebbioso, Marcella; Scarsella, Gianfranco. - In: JOURNAL OF BIOLOGICAL REGULATORS & HOMEOSTATIC AGENTS. - ISSN 0393-974X. - STAMPA. - 28:2(2014), pp. 263-270.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/544129
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