title: Diperoxovanadate can substitute for H(2)O(2) at much lower concentration in inducing features of premature cellular senescence in mouse fibroblasts (NIH3T3).
abstract: Stress induced premature senescence (SIPS) in mammalian cells is an accelerated ageing response and experimentally obtained on treatment of cells with high concentrations of H(2)O(2), albeit at sub-lethal doses, because H(2)O(2) gets depleted by abundant cellular catalase. In the present study diperoxovanadate (DPV) was used as it is known to be stable at physiological pH, to be catalase-resistant and to substitute for H(2)O(2) in its activities at concentrations order of magnitudes lower. On treating NIH3T3 cells with DPV, SIPS-like morphology was observed along with an immediate response of rounding of the cells by disruption of actin cytoskeleton and transient G2/M arrest. DPV could bring about growth arrest and senescence associated features at 25 μM dose, which were not seen with similar doses of either H(2)O(2) or vanadate. A minimal dose of 150 μM of H(2)O(2) was required to induce similar affects as 25 μM DPV. Increase in senescent associated markers such as p21, HMGA2 and PAI-1 was more prominent in DPV treated cells compared to similar dose of H(2)O(2). DPV-treated cells showed marked relocalization of Cyclin D1 from nucleus to cytoplasm. These results indicate that DPV, stable inorganic peroxide, is more efficient in inducing SIPS at lower concentrations compared to H(2)O(2).
authors.affiliation: Laboratory of Cancer Biology, Centre for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad, India.
authors.forename: Nirupama
authors.initials: N
authors.lastname: Chatterjee
authors.forename: Shashi
authors.initials: S
authors.lastname: Kiran
authors.forename: Babul Moni
authors.initials: BM
authors.lastname: Ram
authors.forename: Nashreen
authors.initials: N
authors.lastname: Islam
authors.forename: Tangirala
authors.initials: T
authors.lastname: Ramasarma
authors.forename: Gayatri
authors.initials: G
authors.lastname: Ramakrishna
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D003599:Cytoskeleton / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D016195:G2 Phase / Q000187:drug effects; D006861:Hydrogen Peroxide; D006863:Hydrogen-Ion Concentration; D051379:Mice; D041681:NIH 3T3 Cells; D016877:Oxidants / Q000494:pharmacology*; D010545:Peroxides / Q000494:pharmacology*; D014638:Vanadates / Q000494:pharmacology*
chemical_list: D000199:Actins; D015415:Biomarkers; D016877:Oxidants; D010545:Peroxides; C091767:diperoxovanadate; D014638:Vanadates; D006861:Hydrogen Peroxide; D002374:Catalase