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HPMR

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heat shock protein 90 alpha family class A member 1 OKDB#: 3361
 Symbols: HSP90AA1 Species: human
 Synonyms: EL52, HSPN, LAP2, HSP86, HSPC1, HSPCA, Hsp89, Hsp90, LAP-2, HSP89A, HSP90A, HSP90N, Hsp103, HSPCAL1, HSPCAL4, HEL-S-65p  Locus: 14q32.31 in Homo sapiens


For retrieval of Nucleotide and Amino Acid sequences please go to: OMIM Entrez Gene
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DNA Microarrays
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link to BioGPS
General Comment NCBI Summary: The protein encoded by this gene is an inducible molecular chaperone that functions as a homodimer. The encoded protein aids in the proper folding of specific target proteins by use of an ATPase activity that is modulated by co-chaperones. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]
General function
Comment Immune-mediated destruction of ovarian follicles associated with the presence of HSP90 antibodies. Choudhury A et al. (2015) We previously established that the presence of autoantibodies to heat-shock protein 90 (HSP90) is one common causes of female infertility, and demonstrated that its presence leads to detrimental effects on ovarian and reproductive function in mice. The pathophysiological mechanism and alteration in the immune physiology, however, remain unknown. We therefore carried out detailed analysis of various immune cells in the spleen and ovary following immunization of C57BL/6 female mice to generate antibodies to HSP90 in the general circulation. We observed a significant increase in levels of CD45- cells; CD4+ T cells; Ly6G6C+ cells; and CD11b+ Ly6G+ cells in the spleen of these mice, which correlate with the increased anti-HSP90 antibody production. Ovarian- and granulosa-cell populations also showed increased infiltration of CD45+ leukocytes and neutrophil and monocyte populations, which may have led to the observed ovarian follicular degeneration that predominantly manifested as empty follicles. A decrease in the number of functional ovarian follicles was also associated with a decrease in the level of Gdf9 gene expression. Thus, changes in the immune physiology of the spleen and ovary that leads to the generation of antibodies to HSP90 can also bring about the destruction of ovarian follicles. Mol. Reprod. Dev. 82: 81-89, 2015. © 2015 Wiley Periodicals, Inc.////////////////// HSP90 Antibodies: A Detrimental Factor Responsible for Ovarian Dysfunction. Choudhury A et al. PROBLEM: Earlier studies from our group have established that about 47% cases of autoimmune ovarian failure are due to presence of autoantibodies to Heat Shock Protein 90 (HSP90). However, there are no reports correlating pathological effects of HSP90 autoantibodies leading to ovarian failure. METHOD OF STUDY: Antibodies to HSP90 in female mouse model were generated by active immunization with an immunodominant peptide of HSP90, followed by detailed analysis of several reproductive parameters. RESULT: Estrous cyclicity remains unchanged; however, there was a significant drop in the fertility index due to an increase in pre- and post-implantation loss, associated with an increased incidence of degenerated eggs and embryos. The ovaries showed an increase in the number of empty and degenerated follicles and extensive granulosa cell deaths, which was reflected by the decrease in the levels of Nobox and Gja1 gene expression. CONCLUSION: This study underlines a critical role played by HSP90 in ovarian folliculogenesis and highlights the implications of the presence of anti-HSP90 antibodies in infertile women.
Cellular localization
Comment
Ovarian function Oogenesis, Oocyte maturation
Comment 167 inhibition of heat shock protein 90 reduces developmental competence of bovine oocytes. Souza ED 2013 et al. The 90-kDa heat shock protein (HSP90) is a chaperone that is important for maintaing protein homeostasis under stress conditions. HSP90 seems also to be required for maturation of Xenopus oocytes (Fisher et al. 2000 EMBO J. 19, 1516) and first cleavage of mouse zygotes (Audouard et al. 2011 PloS One 6, e17109). This study aimed to evaluate the effect of inhibition of HSP90 by 17-(allylamino)-17-demethoxygeldanamycin (17AAG, Sigma St. Louis, MO, USA) during in vitro maturation (IVM) on bovine oocyte developmental competence. Immature cumulus-oocyte complexes (COC) were randomly allocated in 3 treatments during IVM: T0 (control; n=240), no HSP90 inhibitor; T1: 2M HSP90 inhibitor (17AAG; n=250) for the first 12h of IVM; and T2: 2M HSP90 inhibitor (n=188) for 24h of IVM. In vitro maturation was performed in Nunc plates containing 400L of TCM-199 medium (Invitrogen, Carlsbad, CA, USA) supplemented with porcine FSH (Hertape Calier, Juatuba, Brazil) and 10% oestrus cow serum under 5% CO2, 95% humidity, and 38.5C for 24h. Oocytes were in vitro fertilized for 20h and incubated under the same IVM conditions. Semen was processed by Percoll gradient (Nutricell, Campinas, Brazil) an IVF performed with 210(6)spermatozoamL(-1). Presumptive zygotes were completely denuded in a PBS solution with hyaluronidase and then cultured in wells with 500L of modified CR2aa medium supplemented with 2.5% fetal calf serum (Nutricell) in an incubator at 38.5C under 5% CO2, 5% O2, 90% N2, and saturated humidity. Cleavage rate was evaluated 72h post-fertilization and blastocyst rates were evaluated at Day 7 and Day 8. Data from 6 repetitions were analysed by generalized linear model procedure of SAS software (version 9.1; SAS Institute Inc., Cary, NC, USA), and means were compared by Student-Newman-Keuls test. Values are shown as means.e.m. There was a tendency (P=0.08) for a lower cleavage rate in T2 (52.65.8%) than in T0 (control; 74.24.1%). Inhibition of HSP90 by 17AAG for 12h and 24h of IVM (T1 and T2, respectively) decreased blastocyst rates at Day 7 (20.43.0% and 14.32.6%, respectively; P<0.01) and Day 8 (22.64.1% and 16.92.7%, respectively; P<0.05) when compared with control (T0=31.82.5% and 34.12.9% for Day 7 and Day 8, respectively). In addition, the inhibition of HSP90 for 24h decreased (P<0.05) the proportion of hatched blastocysts at Day 8 (9.55.0% for T2, respectively) when compared with control (T0=35.83.9%), indicating a reduction on embryo quality. In conclusion, inhibition of HSP90 by 17AAG during IVM results in lower developmental competence, suggesting that this protein is also important for bovine oocytes. Further studies are required to investigate if the role of HSP90 on developmental competence of bovine oocyte is affected when under stress conditions. ///////////////////////// Changes in the expression of Heat Shock Proteins in ovaries from bovines with cystic ovarian disease induced by ACTH. Vel?uez MM 2013 et al. Cystic ovarian disease (COD), which is considered one of the most important causes of reproductive failure in dairy cattle, induces intraovarian changes in the expression of numerous genes. The purpose of this study was to analyze the changes in the expression of Heat Shock Proteins (HSPs) in ovaries from bovines with cystic ovarian disease induced by ACTH. Immunoreactivity for Heat Shock Proteins (HSPs) in ovaries of cows with induced COD showed differential expression patterns in growing follicles from the control group. The immunopositive area for Hsp27 and Hsp60 in granulosa cells showed significant differences between tertiary follicles from normal cycling animals and those from animals with induced COD. The cysts showed increased Hsp27 immunostaining in theca cells in relation to tertiary follicles from normal cycling cows. Hsp70 immunostaining was more intense in cystic follicles than in other follicular categories from animals with induced COD, in both granulosa and theca cells. In granulosa cells, tertiary follicles from the control group showed higher levels of Hsp90 than cysts. These results demonstrate that there are differences in HSP protein expression when COD is induced. In fact, HSP expression would be part of the functional response to the changes in hormones and neurotransmitters induced by stress, indicating that HSPs can control hormonal functions and vice versa. /////////////////////////
Expression regulated by
Comment
Ovarian localization
Comment Levels of heat shock protein transcripts in normal follicles and ovarian follicular cysts. Vel?uez MM et al. In the study, the gene expression of several heat shock proteins (HSPs) was determined in normal follicles and cystic follicles from cattle. A lower expression of HSP10 and HSP40 was observed in granulosa and theca cells of cysts compared to normal follicles. HSP27 was significantly less expressed in granulosa cells in cystic and large antral follicles than in other follicular categories. HSP60 and HSP90a expressions were highest in theca cells of cysts. However, HSP70 and HSP90b exhibited a lower expression in cysts than in healthy follicles.
Follicle stages
Comment
Phenotypes
Mutations 1 mutations

Species: other
Mutation name:
type: null mutation
fertility: infertile - ovarian defect
Comment: Rapid progression through the cell cycle ensures efficient migration of primordial germ cells - The role of Hsp90. Pfeiffer J et al. (2018) Zebrafish primordial germ cells (PGCs) constitute a useful in vivo model to study cell migration and to elucidate the role of specific proteins in this process. Here we report on the role of the heat shock protein Hsp90aa1.2, a protein whose RNA level is elevated in the PGCs during their migration. Reducing Hsp90aa1.2 activity slows down the progression through the cell cycle and leads to defects in the control over the MTOC number in the migrating cells. These defects result in a slower migration rate and compromise the arrival of PGCs at their target, the region where the gonad develops. Our results emphasize the importance of ensuring rapid progression through the cell cycle during single-cell migration and highlight the role of heat shock proteins in the process.//////////////////

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created: July 18, 2006, 11:24 a.m. by: alex   email:
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last update: March 12, 2020, 11:17 a.m. by: hsueh    email:



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