title: Extrathymic production of thymulin induced by oxidative stress, heat shock, apoptosis, or necrosis.
abstract: Thymic peptides are immune regulators produced mainly in the thymus. However, thymic peptides such as thymosin-α and thymopoietin have precursors widely expressed outside the thymus, localized in cell nuclei, and involved in vital nuclear functions. In stress-related conditions, they can relocalize. We hypothesized that another thymic peptide, thymulin, could be similarly produced by non-thymic cells during stress and have a precursor therein. Non-thymic cells, including macrophages and fibroblasts, were exposed to oxidative stress, heat, apoptosis, or necrosis. Extracellular thymulin was identified in media of both cell types 2 h after exposure to stress or lethal signals. Therefore, thymulin is released by non-thymic cells. To examine possible thymulin precursors in non-thymic cells, macrophage lysates were analyzed by western blotting. Bands stained with anti-thymulin antibody were detected in two locations, approximately 60 kDa and 10 kDa, which may be a possible precursor and intermediate. All of the exposures except for heat were effective for induction of the 10 kDa protein. BLAST search using thymulin sequence identified SPATS2L, an intranucleolar stress-response protein with molecular weight of 62 kDa, containing thymulin-like sequence. Comparisons of blots stained with anti-thymulin and anti-SPATS2L antibodies indicate that SPATS2L may be a possible candidate for the precursor of thymulin.
authors.affiliation: Institute of Cell Biophysics, Pushchino, Moscow region, Russia.
authors.forename: Sergey M
authors.initials: SM
authors.lastname: Lunin
authors.affiliation: Institute of Cell Biophysics, Pushchino, Moscow region, Russia.
authors.forename: Maxim O
authors.initials: MO
authors.lastname: Khrenov
authors.affiliation: Institute of Cell Biophysics, Pushchino, Moscow region, Russia.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Glushkova
authors.affiliation: Institute of Cell Biophysics, Pushchino, Moscow region, Russia.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Vinogradova
authors.affiliation: Institute of Cell Biophysics, Pushchino, Moscow region, Russia.
authors.forename: Valery A
authors.initials: VA
authors.lastname: Yashin
authors.affiliation: Institute of Cell Biophysics, Pushchino, Moscow region, Russia.
authors.forename: Evgeny E
authors.initials: EE
authors.lastname: Fesenko
authors.affiliation: Institute of Cell Biophysics, Pushchino, Moscow region, Russia.
authors.forename: Elena G
authors.initials: EG
authors.lastname: Novoselova
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D005347:Fibroblasts / Q000378:metabolism*; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D006358:Hot Temperature; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D009336:Necrosis; D018384:Oxidative Stress; D000067996:RAW 264.7 Cells; D013935:Thymic Factor, Circulating / Q000378:metabolism*
chemical_list: D050884:HSP72 Heat-Shock Proteins; D013935:Thymic Factor, Circulating; D053148:Caspase 3
keywords: SPATS2L; extrathymic production; precursor; thymic peptides; thymulin