title: Age-dependent action of reactive oxygen species on transmitter release in mammalian neuromuscular junctions.
abstract: Reactive oxygen species (ROS) are implicated in aging, but the neurobiological mechanisms of ROS action are not fully understood. Using electrophysiological techniques and biochemical assays, we studied the age-dependent effect of hydrogen peroxide (H2O2) on acetylcholine release in rat diaphragm neuromuscular junctions. H2O2 significantly inhibited both spontaneous (measured as frequency of miniature end-plate potentials) and evoked (amplitude of end-plate potentials) transmitter release in adult rats. The inhibitory effect of H2O2 was much stronger in old rats, whereas in newborns tested during the first postnatal week, H2O2 did not affect spontaneous release from nerve endings and potentiated end-plate potentials. Proteinkinase C activation or intracellular Ca2+ elevation restored redox sensitivity of miniature end-plate potentials in newborns. The resistance of neonates to H2O2 inhibition was associated with higher catalase and glutathione peroxidase activities in skeletal muscle. In contrast, the activities of these enzymes were downregulated in old rats. Our data indicate that the vulnerability of transmitter release to oxidative damage strongly correlates with aging and might be used as an early indicator of senescence.
authors.affiliation: Kazan Institute of Biochemistry and Biophysics, Kazan Scientific Center, Russian Academy of Sciences, Kazan, Russia; Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kazan, Russia. Electronic address: anastasia.shakirzyanova@gmail.com.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Shakirzyanova
authors.affiliation: Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kazan, Russia.
authors.forename: Guzel
authors.initials: G
authors.lastname: Valeeva
authors.affiliation: Kazan State Medical University, Kazan, Russia.
authors.forename: Arthur
authors.initials: A
authors.lastname: Giniatullin
authors.affiliation: A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Nikolay
authors.initials: N
authors.lastname: Naumenko
authors.affiliation: Department of Neuroscience Imaging and Clinical Sciences, University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Fulle
authors.affiliation: Kazan Institute of Biochemistry and Biophysics, Kazan Scientific Center, Russian Academy of Sciences, Kazan, Russia.
authors.forename: Anton
authors.initials: A
authors.lastname: Akulov
authors.affiliation: Institute of Biomedicine, Physiology, University of Eastern Finland, Kuopio, Finland.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Atalay
authors.affiliation: Kazan Institute of Biochemistry and Biophysics, Kazan Scientific Center, Russian Academy of Sciences, Kazan, Russia; Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kazan, Russia; Kazan State Medical University, Kazan, Russia.
authors.forename: Eugeny
authors.initials: E
authors.lastname: Nikolsky
authors.affiliation: Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kazan, Russia; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Rashid
authors.initials: R
authors.lastname: Giniatullin
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D003964:Diaphragm / Q000294:innervation; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D009469:Neuromuscular Junction / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D018377:Neurotransmitter Agents; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D011493:Protein Kinase C; D000109:Acetylcholine; D002118:Calcium
keywords: Acetylcholine release; Aging; Neuromuscular; Newborn; Reactive oxygen species