title: Antiapoptotic role of S-adenosyl-l-methionine against hydrochloric acid induced cell death in Saccharomyces cerevisiae.
abstract: Exposure of stationary phase cells of Saccharomyces cerevisiae to 10 mM HCl (pH approximately 2) resulted in cell death as a function of time (up to 6 h) with most (about 40%-65%) of the cells showing apoptotic features including chromatin condensation along the nuclear envelope, exposure of phosphatidylserine on the outer leaflet of cytoplasmic membrane, and DNA fragmentation. During the first 2 h of acid exposure there was an increase in reactive oxygen species (ROS) level inside cells, with subsequent elevation in the level of lipid peroxidation and decrease in reducing equivalents culminating in loss of mitochondrial membrane potential (DeltaPsi(m)). An initial (1 h) event of mitochondrial hyper-polarization with subsequent elevation of ROS level of the acid treated cells was also observed. S-adenosyl-l-methionine (AdoMet; 1 mM) treatment increased the cell survival of the acid stressed cells. It partially scavenged the increased intracellular ROS level by supplementing glutathione through the transsulfuration pathway. It also inhibited acid mediated lipid peroxidation, partially recovered acid evoked loss of DeltaPsi(m) and protected the cells from apoptotic cell death. S-adenosyl di-aldehyde, an indirect inhibitor of the AdoMet metabolic pathway, increased mortality of the acid treated cells. Incubation of acid stressed cells with the antioxidant, N-acetyl-cysteine (1 mM), decreased the cellular mortality, but the same concentration of AdoMet offered more protection by scavenging the free radicals. The ability of AdoMet to scavenge ROS mediated apoptosis may be an important function of this molecule in responding to cellular stress. The study could open a new avenue for detailed investigation on the curative potential of AdoMet against gastric ulcer.
authors.affiliation: Department of Biotechnology, Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Kolkata 700032, India.
authors.forename: Dipankar
authors.initials: D
authors.lastname: Malakar
authors.forename: Anindya
authors.initials: A
authors.lastname: Dey
authors.forename: Arghya
authors.initials: A
authors.lastname: Basu
authors.forename: Anil K
authors.initials: AK
authors.lastname: Ghosh
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002374:Catalase / Q000378:metabolism; D005978:Glutathione / Q000032:analysis; D006851:Hydrochloric Acid / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D015227:Lipid Peroxidation / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000648:ultrastructure; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
chemical_list: D017382:Reactive Oxygen Species; D012436:S-Adenosylmethionine; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D006851:Hydrochloric Acid