title: Degenerative events in retina and optic nerve induced by inhibition of carnitine transport.
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.
authors.affiliation: Department of Cardiovascular, Respiratory, Nephrology, Geriatric and Anesthetic Sciences, Sapienza University of Rome, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Pescosolido
authors.affiliation: Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Pascarella
authors.affiliation: Department of Sense Organs, Sapienza University of Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Nebbioso
authors.affiliation: Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Scarsella
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001693:Biological Transport, Active / Q000187:drug effects; D002317:Cardiovascular Agents / Q000009:adverse effects* / Q000494:pharmacology; D002331:Carnitine / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D008297:Male; D008763:Methylhydrazines / Q000009:adverse effects* / Q000494:pharmacology; D009901:Optic Nerve Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012162:Retinal Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002317:Cardiovascular Agents; D008763:Methylhydrazines; C050147:3-(2,2,2-trimethylhydrazine)propionate; C505410:Casp3 protein, rat; D053148:Caspase 3; D002331:Carnitine