Abstract:
BACKGROUND:Spermatic cord torsion can lead to testis ischemia (I) and subsequent ischemia-reperfusion (I/R) causing germ cell-specific apoptosis. Previously, we demonstrated that the hypoxia-inducible factor-1 (HIF-1) transcription factor, a key regulator of physiological responses to hypoxia, is abundant in Leydig cells in normoxic and ischemic testes. We hypothesize that testicular HIF-1 activates the expression of antiapoptotic target genes to protect Leydig cells from apoptosis. In silico analysis of testis genes containing a consensus hypoxia response element (HRE, 5'-RCGTG-3') identified myeloid cell leukemia-1 (Mcl-1) as a potential HIF-1 target gene. The purpose of this study was to determine whether HIF-1 shows DNA-binding activity in normoxic and ischemic testes and whether Mcl-1 is a target gene of testicular HIF-1. METHODS:The testicular HIF-1 DNA-binding capacity was analyzed in vitro using a quantitative enzyme-linked immunosorbent assay (ELISA) and electrophoretic mobility shift assays (EMSA). MCL-1 protein expression was evaluated by immunoblot analysis and immunohistochemistry. The binding of testicular HIF-1 to the Mcl-1 gene was examined via chromatin immunoprecipitation (ChIP) analysis. RESULTS:The ELISA and EMSA assays demonstrated that testicular HIF-1 from normoxic and ischemic testes binds DNA equally strongly, suggesting physiological roles for HIF-1 in the normoxic testis, unlike most tissues in which HIF-1 is degraded under normoxic conditions and is only activated by hypoxia. MCL-1 protein was determined to be abundant in both normoxic and ischemic testes and expressed in Leydig cells. In a pattern identical to that of HIF-1 expression, the steady-state levels of MCL-1 were not significantly affected by I or I/R and MCL-1 co-localized with HIF-1α in Leydig cells. Chromatin immunoprecipitation (ChIP) analysis using a HIF-1 antibody revealed sequences enriched for the Mcl-1 promoter. CONCLUSIONS:The results demonstrated that, unlike what is observed in most tissues, HIF-1 displays DNA-binding activity in both normoxic and ischemic testes, and Mcl-1 may be a key target gene of testicular HIF-1 with potential roles in the antiapoptotic protection of Leydig cells.
journal_name
Reprod Biol Endocrinoljournal_title
Reproductive biology and endocrinology : RB&Eauthors
Palladino MA,Shah A,Tyson R,Horvath J,Dugan C,Karpodinis Mdoi
10.1186/1477-7827-10-104subject
Has Abstractpub_date
2012-12-05 00:00:00pages
104issn
1477-7827pii
1477-7827-10-104journal_volume
10pub_type
杂志文章abstract:BACKGROUND:Seminal plasma serves as a natural reservoir of antioxidants. It helps to remove excessive formation of reactive oxygen species (ROS) and consequently, reduce oxidative stress. Proteomic profiling of seminal plasma proteins is important to understand the molecular mechanisms underlying oxidative stress and s...
journal_title:Reproductive biology and endocrinology : RB&E
pub_type: 杂志文章
doi:10.1186/1477-7827-11-85
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journal_title:Reproductive biology and endocrinology : RB&E
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journal_title:Reproductive biology and endocrinology : RB&E
pub_type: 杂志文章,多中心研究
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journal_title:Reproductive biology and endocrinology : RB&E
pub_type: 杂志文章,评审
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journal_title:Reproductive biology and endocrinology : RB&E
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journal_title:Reproductive biology and endocrinology : RB&E
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doi:10.1186/s12958-020-00622-y
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journal_title:Reproductive biology and endocrinology : RB&E
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journal_title:Reproductive biology and endocrinology : RB&E
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journal_title:Reproductive biology and endocrinology : RB&E
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journal_title:Reproductive biology and endocrinology : RB&E
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journal_title:Reproductive biology and endocrinology : RB&E
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doi:10.1186/1477-7827-9-109
更新日期:2011-08-03 00:00:00
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journal_title:Reproductive biology and endocrinology : RB&E
pub_type: 杂志文章
doi:10.1186/1477-7827-4-58
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journal_title:Reproductive biology and endocrinology : RB&E
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doi:10.1186/s12958-015-0060-x
更新日期:2015-07-03 00:00:00
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journal_title:Reproductive biology and endocrinology : RB&E
pub_type: 杂志文章
doi:10.1186/1477-7827-11-47
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journal_title:Reproductive biology and endocrinology : RB&E
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journal_title:Reproductive biology and endocrinology : RB&E
pub_type: 杂志文章
doi:10.1186/1477-7827-12-44
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journal_title:Reproductive biology and endocrinology : RB&E
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journal_title:Reproductive biology and endocrinology : RB&E
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journal_title:Reproductive biology and endocrinology : RB&E
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journal_title:Reproductive biology and endocrinology : RB&E
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journal_title:Reproductive biology and endocrinology : RB&E
pub_type: 杂志文章
doi:10.1186/1477-7827-8-104
更新日期:2010-08-26 00:00:00
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journal_title:Reproductive biology and endocrinology : RB&E
pub_type: 杂志文章
doi:10.1186/s12958-015-0136-7
更新日期:2016-01-15 00:00:00
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journal_title:Reproductive biology and endocrinology : RB&E
pub_type: 杂志文章
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journal_title:Reproductive biology and endocrinology : RB&E
pub_type: 杂志文章
doi:10.1186/1477-7827-7-128
更新日期:2009-11-19 00:00:00
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journal_title:Reproductive biology and endocrinology : RB&E
pub_type: 杂志文章,评审
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更新日期:2020-06-06 00:00:00
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journal_title:Reproductive biology and endocrinology : RB&E
pub_type: 杂志文章
doi:10.1186/s12958-017-0299-5
更新日期:2017-10-03 00:00:00
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journal_title:Reproductive biology and endocrinology : RB&E
pub_type: 杂志文章
doi:10.1186/s12958-018-0344-z
更新日期:2018-07-05 00:00:00
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journal_title:Reproductive biology and endocrinology : RB&E
pub_type: 杂志文章
doi:10.1186/s12958-019-0452-4
更新日期:2019-01-11 00:00:00
abstract:BACKGROUND:Secreted protein of Ly-6 domain 1 (SOLD1), a secretory-type member of the Ly-6 superfamily, is expressed in both fetal and maternal tissues throughout gestation. SOLD1 mRNA is expressed in the endometrium and in trophoblast mononucleate and binucleate cells, suggesting it plays an important role not only in ...
journal_title:Reproductive biology and endocrinology : RB&E
pub_type: 杂志文章
doi:10.1186/1477-7827-12-55
更新日期:2014-06-21 00:00:00
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journal_title:Reproductive biology and endocrinology : RB&E
pub_type: 杂志文章
doi:10.1186/1477-7827-7-93
更新日期:2009-09-07 00:00:00