DEFINITION
A short protein description with the molecular wheight, isoforms, etc...
Use, when available, the link to Wikipedia (Es Trypsin)
External links not available on Wikipedia have to be added here
THE GENE
Wikigenes includes links to
- NCBI Gene
- NCBI SNP
- iHOP resource
- OMIM
- SNPedia
- UniProt
- Ensembl
- HGNC
CHEMICAL STRUCTURE AND IMAGES
When relevant for the function
- Primary structure
- Secondary structure
- Tertiary structure
- Quaternary structure
h4. Protein Aminoacids Percentage (Width 700 px)
SYNTHESIS AND TURNOVER
mRNA synthesis
protein synthesis
post-translational modifications
degradation
CELLULAR FUNCTIONS
ESTROGEN EFFECTS ON ATROPHIC SKELETAL MUSCLE, 2008
Abstract Text:
DESCRIPTION (provided by applicant): In the physical rehabilitation setting, women typically demonstrate lesser return to function than men. Estrogen (E2) deficiency might contribute to the gender discrepancy, as low E2 levels have been linked to a decrease in lean muscle mass. Of the more than two million women receiving post-operative or rehabilitation care each year, approximately 1/2 of them are "estrogen-deficient" due to natural menopause, surgical menopause, and normal hormonal rhythms disrupted by illness or trauma. The overall goal of this translational research project is to use animal models to determine if exogenous E2 should be considered as an adjunct to standard physical rehabilitation for E2 deficient women. Prior studies in animals have demonstrated that a lack of circulating E2 (subsequent to ovariectomy (OVX)) impairs recovery of laboratory-induced atrophic skeletal muscle. Failure to regrow atrophied muscles in OVX rats was associated with failure to initiate protein synthesis. In contrast, E2 deficient rats with muscle atrophy that were given E2 hormone replacement therapy (HRT) demonstrated nearly complete regrowth of atrophied muscle within a week. Muscle regrowth with E2 HRT is associated with activation of the Akt/mTOR pathway of muscle protein synthesis. Moreover, E2 HRT restored myofiber cross-sectional area. The proposed project will elucidate mechanisms associated with the failure to regrow atrophied skeletal muscle in the E2 deficient female rat. We will conduct experiments that examine skeletal muscle regrowth for the E2-deficient rats receiving short-term E2 HRT and standard physical rehabilitation exercise. We will also examine the components of muscle regrowth (e.g., cross-sectional area). The specific aims are to: 1) determine the extent of atrophic skeletal muscle regrowth produced independently by E2 HRT or rehabilitation exercise in E2 deficient rats. 2) Determine if E2 HRT combined with rehabilitation exercise can augment the extent of atrophic skeletal muscle regrowth in E2 deficient rats. 3) Use estrogen receptor (ER) knock-out mice and ER-specific ligands to determine if the E2 effect on atrophic muscle regrowth is mediated through the ER1 or ER2 receptor. Concerns about the safety of E2 HRT compel investigation of an ER specific compound that will prove effective without undesirable side-effects. The proposed studies will lay the groundwork for determining the extent to which short-term estrogen (E2) therapy should be considered as an adjunct to standard physical rehabilitation care for estrogen deficient women. PUBLIC HEALTH RELEVANCE: Approximately 1/2 of the adult female population may be considered estrogen deficient due to menopause, surgery, trauma or illness. Estrogen deficiency has been linked to a decrease in lean muscle mass and impaired muscle regrowth following extended bed rest. Short-term estrogen hormone replacement therapy could provide a valuable addition to rehabilitation exercise protocols, but more information about the role and mechanism of estrogen effectiveness in skeletal muscle is needed.
Estrogen receptor-alpha and -beta and aromatase knockout effects on lower limb muscle mass and contractile function in female mice. 2009
Brown M1, Ning J, Ferreira JA, Bogener JL, Lubahn DB.
Author information
Abstract
Estrogen (E2) is reported to regulate skeletal muscle mass and contractile function; whether E2 exerts its effects through estrogen receptor-alpha (ERalpha) or -beta (ERbeta) is unclear. We determined the effect of ERalpha or ERbeta elimination on muscle mass and contractile function in multiple muscles of the lower limb, muscles with different locomotor tasks and proportions of fiber types I and II: soleus (Sol), plantaris (Plan), tibialis anterior (TA), and gastrocnemius (Gast) in mature female mice. To determine E2 elimination effects on muscle, we also used aromatase (Ar) knockout (KO) and wild-type (WT) mice. ERalpha and ArKO body weights were approximately 10 and 20% higher than WT. Although muscle mass tended to show a commensurate increase in both groups, only the TA was significantly larger in ERalpha (P<0.05). Ratios of muscle mass to body mass revealed significantly lower values for Gast and TA in ArKO mice (P<0.05). Tetanic tension (Po) per calculated anatomical cross-sectional area (aCSA) in ERalpha KO was lower in TA and Gast than in WT. Lower Po/aCSA in ERalpha KO Gast and TA was also supported histologically by significantly less Po/fiber areas (P<0.05). ArKO mice also had lower Po/aCSA in Gast and TA compared with WT. ERbeta KO and WT mice were comparable in all measures. Our results support the hypothesis that E2 effects on skeletal muscle are mediated in part via the ERalpha but that E2 effects may be mediated via more than one mechanism or receptor.
cellular localization,
Sex-specific mTOR signaling determines sexual dimorphism in myocardial adaptation in normotensive DOCA-salt model. 2013
Abstract
The deoxycorticosterone acetate (DOCA)-salt mouse model exhibits adverse cardiac remodeling in male mice and cardiac protection in female mice, even when blood pressure is normalized. We hypothesized that intact mammalian target of rapamycin (mTOR) signaling is necessary for cardiac protection in females. We first tested sex differences and intracellular signaling after mTOR targeting with rapamycin in wild-type mice. Radio-telemetric blood pressure was maintained at normal for 6 weeks. Rapamycin significantly reduced left ventricular hypertrophy, preserved ejection fraction, inhibited fibrosis, and maintained capillary structure in male mice. Decreased mTORC1 and increased mTORC2 activity were detected in rapamycin-treated male mice compared with vehicle controls. In contrast, female mice developed dilative left ventricular hypertrophy, cardiac fibrosis, and capillary loss similar to DOCA-salt females lacking the estrogen receptor β (ERβ(-/-)) that we described earlier. Because rapamycin downregulated ERβ in female mice, we next studied ERβ(-/-) normotensive DOCA-salt females. Vehicle-treated wild-type females maintained their high constitutive mTORC1 and mTORC2 in response to DOCA-salt. In contrast to males, both mTORCs were decreased by rapamycin, in particular mTORC2 by 60%. ERβ(-/-) DOCA-salt females showed similar mTORC1 and mTORC2 response patterns. We suggest that ERβ-dependent regulation involves sex-specific use of mTOR signaling branches. Maintenance of both mTORC1 and mTORC2 signaling seems to be essential for adaptive cardiac remodeling in females and supports a rationale for sex-specific therapeutic strategies in left ventricular hypertrophy.
Estrogen receptor-beta signals left ventricular hypertrophy sex differences in normotensive deoxycorticosterone acetate-salt mice. 2011
We found earlier that deoxycorticosterone acetate-salt treatment causes blood pressure-independent left ventricular hypertrophy, but only in male mice. To test the hypothesis that the estrogen receptor-β (ERβ) protects the females from left ventricular hypertrophy, we treated male and female ERβ-deficient (ERβ(-/-)) mice and their male and female littermates (wild-type [WT]) with deoxycorticosterone acetate-salt and made them telemetrically normotensive with hydralazine. WT males had increased (+16%) heart weight/tibia length ratios compared with WT females (+7%) at 6 weeks. In ERβ(-/-) mice, this situation was reversed. Female WT mice had the greatest heart weight/tibia length ratio increases of all of the groups (+23%), even greater than ERβ(-/-) males (+10%). Echocardiography revealed concentric left ventricular hypertrophy in male WT mice, whereas ERβ(-/-) females developed dilative left ventricular hypertrophy. The hypertrophic response in female ERβ(-/-) mice was accompanied by the highest degree of collagen deposition, indicating maladaptive remodeling. ERβ(+/+) females showed robust protective p38 and extracellular signal-regulated kinase 1/2 signaling relationships compared with other groups. Calcineurin Aβ expression and its positive regulator myocyte-enriched calcineurin-interacting protein 1 were increased in deoxycorticosterone acetate-salt female ERβ(-/-) mice, yet lower than in WT males. Endothelin increased murine cardiomyocyte hypertrophy in vitro, which could be blocked by estradiol and an ERβ agonist. We conclude that a functional ERβ is essential for inducing adaptive p38 and extracellular signal-regulated kinase signaling, while reducing maladaptive calcineurin signaling in normotensive deoxycorticosterone acetate female mice. Our findings address the possibility of sex-specific cardiovascular therapies.
The failure to degrade JunB contributes to Collagen type I over-production and dermal fibrosis in Scleroderma. 2014
Abstract
Objectives: The excessive deposition of extracellular matrix including collagen type I is a key aspect in the pathogenesis of connective tissue diseases such as Scleroderma (SSc). To further our understanding of the mechanisms governing the dysregulation of type I collagen production in SSc, we investigated the role of the activator protein 1 (AP1) family of transcription factors in regulating collagen gene (COL1A2) transcription. Methods: The expression and nuclear localization of AP1 family members (c-Jun, JunB, JunD, Fra 1 and 2 and c-Fos) was examined in dermal biopsies and explanted skin fibroblasts from diffuse cutaneous SSc and healthy controls by immunohistochemistry and western blotting. Gene activation was determined by assessing the interaction of transcription factors with the COL1A2 enhancer using transient transfection of reporter gene constructs, electrophoretic mobility shift assays, chromatin immune-precipitation analysis and RNA interference, knocking down individual AP1 family members. Inhibition of fibroblast mTOR, AKT and GSK3β signalling pathways was achieved using small molecule pharmacological inhibitors. Results: JunB binds the COL1A2 enhancer and directs its coalescence with the proximal promoter activating gene transcription. Knockdown of JunB reduces enhancer activation and COL1A2 expression in response to TGFβ. In SSc, increased mTOR/AKT signalling inactivates GSK3β, leading to a block in JunB degradation and hence constitutively high JunB expression. Conclusions: In SSc, JunB accumulation due to altered mTOR/AKT signalling and a failure of proteolytic degradation underpins the aberrant type I collagen overexpression. The data identifies JunB as a potential target for anti-fibrotic therapy in SSc
biological function
- Cell signaling and Ligand transport
- Structural proteins
REGULATION
DIAGNOSTIC USE
