title: Lipocalin 2 regulation by thermal stresses: protective role of Lcn2/NGAL against cold and heat stresses.
abstract: Environmental temperature variations are the most common stresses experienced by a wide range of organisms. Lipocalin 2 (Lcn2/NGAL) is expressed in various normal and pathologic conditions. However, its precise functions have not been fully determined. Here we report the induction of Lcn2 by thermal stresses in vivo, and its role following exposure to cold and heat stresses in vitro. Induction of Lcn2 in liver, heart and kidney was detected by RT-PCR, Western blot and immunohistochemistry following exposure of mice to heat and cold stresses. When CHO and HEK293T cells overexpressing NGAL were exposed to cold stress, cell proliferation was higher compared to controls. Down-regulatrion of NGAL by siRNA in A549 cells resulted in less proliferation when exposed to cold stress compared to control cells. The number of apoptotic cells and expression of pro-apoptotic proteins were lower in the NGAL overexpressing CHO and HEK293T cells, but were higher in the siRNA-transfected A549 cells compared to controls, indicating that NGAL protects cells against cold stress. Following exposure of the cells to heat stress, ectopic expression of NGAL protected cells while addition of exogenous recombinant NGAL to the cell culture medium exacerbated the toxicity of heat stress specially when there was low or no endogenous expression of NGAL. It had a dual effect on apoptosis following heat stress. NGAL also increased the expression of HO-1. Lcn2/NGAL may have the potential to improve cell proliferation and preservation particularly to prevent cold ischemia injury of transplanted organs or for treatment of some cancers by hyperthermia.
authors.affiliation: Research Center, Iranian Blood Transfusion Organization, Tehran, Iran. roudkenar@ibto.ir
authors.forename: Mehryar Habibi
authors.initials: MH
authors.lastname: Roudkenar
authors.forename: Raheleh
authors.initials: R
authors.lastname: Halabian
authors.forename: Amaneh Mohammadi
authors.initials: AM
authors.lastname: Roushandeh
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Nourani
authors.forename: Nasser
authors.initials: N
authors.lastname: Masroori
authors.forename: Majid
authors.initials: M
authors.lastname: Ebrahimi
authors.forename: Mahin
authors.initials: M
authors.lastname: Nikogoftar
authors.forename: Mehdi
authors.initials: M
authors.lastname: Rouhbakhsh
authors.forename: Parisa
authors.initials: P
authors.lastname: Bahmani
authors.forename: Ali Jahanian
authors.initials: AJ
authors.lastname: Najafabadi
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Shokrgozar
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D016466:CHO Cells; D045744:Cell Line, Tumor; D003080:Cold Temperature; D006224:Cricetinae; D003412:Cricetulus; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology; D055785:Gene Knockdown Techniques; D018882:Heat Stress Disorders / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007035:Hypothermia / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D000209:Acute-Phase Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C071332:Lcn2 protein, mouse; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1