The nuclear import factor importin α4 can protect against oxidative stress

Autor: Jennifer D. Ly-Huynh, Yoshihiro Yoneda, David A. Jans, Kate L Loveland, Peter Koopman, Julia Young, Cate Browne, Yoichi Miyamoto, Helen E Lescesen
Rok vydání: 2013
Předmět:
Male
Spermatocyte
Immunoenzyme Techniques
Mice
0302 clinical medicine
Cellular stress response
Testis
Importin/karyopherin
Protamines
Promoter Regions
Genetic
0303 health sciences
030219 obstetrics & reproductive medicine
Cell Differentiation
Flow Cytometry
Spermatids
Blotting
Southern
medicine.anatomical_structure
Nuclear transport
Genetically modified mouse
alpha Karyopherins
Transgene
Recombinant Fusion Proteins
Blotting
Western
Green Fluorescent Proteins
Active Transport
Cell Nucleus
Mice
Transgenic
Biology
Real-Time Polymerase Chain Reaction
03 medical and health sciences
medicine
Animals
Humans
Immunoprecipitation
Spermatogenesis
Molecular Biology
030304 developmental biology
Cell Proliferation
Cell Nucleus
Spermatid
Cell Biology
DNA
Molecular biology
Embryonic stem cell
Fusion protein
Mice
Inbred C57BL
Oxidative Stress
Fertility
Germ Cells
Mice
Inbred CBA
Nuclear localization sequence
Zdroj: Biochimica et biophysica acta. 1833(10)
ISSN: 0006-3002
Popis: The importin (IMP) superfamily of nuclear transport proteins is essential to key developmental pathways, including in the murine testis where expression of the 6 distinct IMPα proteins is highly dynamic. Present predominantly from the spermatocyte stage onwards, IMPα4 is unique in showing a striking nuclear localization, a property we previously found to be linked to maintenance of pluripotency in embryonic stem cells and to the cellular stress response in cultured cells. Here we examine the role of IMPα4 in vivo for the first time using a novel transgenic mouse model in which we overexpress an IMPα4–EGFP fusion protein from the protamine 1 promoter to recapitulate endogenous testicular germ cell IMPα4 expression in spermatids. IMPα4 overexpression did not affect overall fertility, testis morphology/weight or spermatogenic progression under normal conditions, but conferred significantly (> 30%) increased resistance to oxidative stress specifically in the spermatid subpopulation expressing the transgene. Consistent with a cell-specific role for IMPα4 in protecting against oxidative stress, haploid germ cells from IMPα4 null mice were significantly (c. 30%) less resistant to oxidative stress than wild type controls. These results from two unique and complementary mouse models demonstrate a novel protective role for IMPα4 in stress responses specifically within haploid male germline cells, with implications for male fertility and genetic integrity.
Databáze: OpenAIRE
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