Role of the cytoskeleton in steroidogenesis

2021 ◽  
Vol 21 ◽  
Author(s):  
Zaichao Wu ◽  
Chunping Zhang
Keyword(s):  
Signaling Pathways ◽  
Outer Membrane ◽  
Intracellular Camp ◽  
Enzymatic Reactions ◽  
Related Factors ◽  
Steroid Synthesis ◽  
Mitochondrial Movement ◽  
Camp Pathway ◽  
Rate Limiting Step ◽  
Cytoskeletal Network

: Steroidogenesis in the adrenal cortex or gonads is a complicated process, modulated by various elements either at the tissue or molecular level. The substrate—cholesterol is first delivered to the outer membrane of mitochondria, undergoing a series of enzymatic reactions along with the material exchange between the mitochondria and the ER (endoplasmic reticulum) and ultimately yield various steroids: aldosterone, cortisol, testosterone and estrone. Several valves are set to adjust the amount of production to the needs. e.g. StAR(steroidogenic acute regulator) is in charge of the rate-limiting step—traffic of cholesterol from outer membrane to inner membrane of mitochondria. And the “needs” is partly reflected by trophic signals like ACTH、LH and downstream pathways-- intracellular cAMP pathway, which represents the endocrinal regulation of steroid synthesis, too. The coordinated activities of these related factors are all associated with another crucial cellular constituent—the cytoskeleton, which plays a crucial role in the cellular architecture and substrate trafficking. Though considerable studies have been performed regarding steroid synthesis, details about the upstream signaling pathways and mechanisms of the regulation by cytoskeleton network still remain unclear. The metabolism and interplays of the pivotal cellular organelles with cytoskeleton are worth exploring as well. In this review, we summarize research of different time span, describing the roles of specific cytoskeleton elements in steroidogenesis and related signaling pathways involved in the steroid synthesis. In addition, we discussed the inner cytoskeletal network involved in steroidogenic processes such as mitochondrial movement, organelle interactions and cholesterol trafficking.

scholarly journals Bacterial tail anchors can target to the mitochondrial outer membrane

2017 ◽  
Author(s):  
Güleycan Lutfullahoğlu Bal ◽  
Abdurrahman Keskin ◽  
Ayşe Bengisu Seferoğlu ◽  
Cory D. Dunn
Keyword(s):  
Outer Membrane ◽  
Protein Translocation ◽  
Mitochondrial Protein ◽  
Eukaryotic Cell ◽  
Eukaryotic Cells ◽  
Mitochondrial Outer Membrane ◽  
Bacterial Proteins ◽  
Rate Limiting Step ◽  
Protein Entry ◽  
Rate Limiting

ABSTRACTDuring the generation and evolution of the eukaryotic cell, a proteobacterial endosymbiont was refashioned into the mitochondrion, an organelle that appears to have been present in the ancestor of all present-day eukaryotes. Mitochondria harbor proteomes derived from coding information located both inside and outside the organelle, and the rate-limiting step toward the formation of eukaryotic cells may have been development of an import apparatus allowing protein entry to mitochondria. Currently, a widely conserved translocon allows proteins to pass from the cytosol into mitochondria, but how proteins encoded outside of mitochondria were first directed to these organelles at the dawn of eukaryogenesis is not clear. Because several proteins targeted by a carboxyl-terminal tail anchor (TA) appear to have the ability to insert spontaneously into the mitochondrial outer membrane (OM), it is possible that self-inserting, tail-anchored polypeptides obtained from bacteria might have formed the first gate allowing proteins to access mitochondria from the cytosol. Here, we tested whether bacterial TAs are capable of targeting to mitochondria. In a survey of proteins encoded by the proteobacterium Escherichia coli, predicted TA sequences were directed to specific subcellular locations within the yeast Saccharomyces cerevisiae. Importantly, TAs obtained from DUF883 family members ElaB and YqjD were abundantly localized to and inserted at the mitochondrial OM. Our results support the notion that eukaryotic cells are able to utilize membrane-targeting signals present in bacterial proteins obtained by lateral gene transfer, and our findings make plausible a model in which mitochondrial protein translocation was first driven by tail-anchored proteins.

scholarly journals Role of vaspin in porcine ovary: effect on signaling pathways and steroid synthesis via GRP78 receptor and protein kinase A†

2020 ◽  
Vol 102 (6) ◽  
pp. 1290-1305 ◽  
Author(s):  
Patrycja Kurowska ◽  
Ewa Mlyczyńska ◽  
Monika Dawid ◽  
Joelle Dupont ◽  
Agnieszka Rak
Keyword(s):  
Protein Kinase ◽  
Western Blot ◽  
Protein Kinase A ◽  
Signaling Pathways ◽  
Dependent Manner ◽  
Steroid Synthesis ◽  
Ovarian Cells ◽  
Vitro Effect ◽  
Kinase A

Abstract Vaspin, visceral-adipose-tissue-derived serine protease inhibitor, is involved in the development of obesity, insulin resistance, inflammation, and energy metabolism. Our previous study showed vaspin expression and its regulation in the ovary; however, the role of this adipokine in ovarian cells has never been studied. Here, we studied the in vitro effect of vaspin on various kinase-signaling pathways: mitogen-activated kinase (MAP3/1), serine/threonine kinase (AKT), signal transducer and activator of transcription 3 (STAT3) protein kinase AMP (PRKAA1), protein kinase A (PKA), and on expression of nuclear factor kappa B (NFKB2) as well as on steroid synthesis by porcine ovarian cells. By using western blot, we found that vaspin (1 ng/ml), in a time-dependent manner, increased phosphorylation of MAP3/1, AKT, STAT3, PRKAA1, and PKA, while it decreased the expression of NFKB2. We observed that vaspin, in a dose-dependent manner, increased the basal steroid hormone secretion (progesterone and estradiol), mRNA and protein expression of steroid enzymes using real-time PCR and western blot, respectively, and the mRNA of gonadotropins (FSHR, LHCGR) and steroids (PGR, ESR2) receptors. The stimulatory effect of vaspin on basal steroidogenesis was reversed when ovarian cells were cultured in the presence of a PKA pharmacological inhibitor (KT5720) and when GRP78 receptor was knocked down (siRNA). However, in the presence of insulin-like growth factor type 1 and gonadotropins, vaspin reduced steroidogenesis. Thus, vaspin, by activation of various signaling pathways and stimulation of basal steroid production via GRP78 receptor and PKA, could be a new regulator of porcine ovarian function.

scholarly journals Developmental Dependence on NurRE and EboxNeuro for Expression of Pituitary Proopiomelanocortin

2008 ◽  
Vol 22 (7) ◽  
pp. 1647-1657 ◽  
Author(s):  
Pierre-Luc Lavoie ◽  
Lionel Budry ◽  
Aurélio Balsalobre ◽  
Jacques Drouin
Keyword(s):  
Signaling Pathways ◽  
Regulatory Element ◽  
Regulatory Elements ◽  
Portal System ◽  
Orphan Nuclear Receptors ◽  
Related Factors ◽  
Specific Expression ◽  
Pituitary Development ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix

Abstract Cell-specific expression of the pituitary proopiomelanocortin (POMC) gene depends on the combinatorial action of a large number of DNA-binding transcription factors (TFs). These include general and cell-restricted factors, as well as factors that act as effectors of signaling pathways. We have previously defined in the distal POMC promoter a composite regulatory element that contains targets for basic helix-loop-helix TFs conferring cell specificity and for NGFI-B orphan nuclear receptors that are responsive to CRH signaling and to glucocorticoid negative feedback. These factors act on neighboring regulatory elements, the EboxNeuro and NurRE, respectively. Currently, the EboxNeuro is thought to be the target of NeuroD1 during fetal development, but this factor may not account for activity in the adult pituitary; it is also unknown whether the NurRE and NGFI-B-related factors are active before establishment of the hypothalamic-pituitary portal system. In order to assess the importance of these regulatory elements and their cognate TFs throughout pituitary organogenesis and in the adult, we have assessed the activity of mutant POMC promoters in transgenic mice throughout development. These experiments indicate that the EboxNeuro and cognate basic helix-loop-helix factors are required throughout development and in the adult gland, beyond expression of NeuroD1. Similarly, the data reveal sustained importance of the NurRE and its cognate factors throughout pituitary development. These data contrast the sustained dependence throughout development on the same regulatory elements with the highly dynamic patterns of TF expression and the modulation of their activity in response to signaling pathways.

Dibutyryl cAMP induces a gestation-dependent absorption of fetal lung liquid

1990 ◽  
Vol 68 (5) ◽  
pp. 2054-2059 ◽  
Author(s):  
D. V. Walters ◽  
C. A. Ramsden ◽  
R. E. Olver
Keyword(s):  
Fetal Lung ◽  
Liquid Volume ◽  
Intracellular Camp ◽  
Maximal Effect ◽  
Dibutyryl Camp ◽  
Rate Limiting Step ◽  
Liquid Absorption ◽  
Dependent Absorption ◽  
Lung Liquid ◽  
Rate Limiting

The maturation of the adenosine 3′,5′-cyclic monophosphate-(cAMP) dependent pathway controlling fetal lung liquid secretion was examined in experiments in which the lungs of chronically catheterized fetal lambs (123-141 days gestational age) were exposed to dibutyryl cAMP (DBcAMP, 10(-4) M). The effect of DBcAMP was markedly gestation dependent, with the greatest effect observed in the most mature fetuses. In immature fetuses (less than 130 days, mean age 125 days) DBcAMP caused slowing of secretion, with maximal effect at 5 h. With increasing maturity the effect of DBcAMP was more pronounced and occurred earlier so that in mature fetuses (mean age 140 days) lung liquid absorption took place, with maximal effect at 2 h. Changes in lung liquid volume flow induced by DBcAMP could be blocked by addition of 10(-4) M amiloride to lung liquid. It is concluded that 1) DBcAMP induces a change in lung liquid secretion that, like epinephrine, is mediated via an increase in Na+ permeability of the apical membrane of the lung epithelium and 2) the rate-limiting step in the maturation of this process must lie beyond the generation of intracellular cAMP.

Evaluating oncogenic pathway dysregulation in adolescents and young adults with acute myeloid leukemia.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7107-7107
Author(s):  
Arati Rao ◽  
John Andy Livingston ◽  
Sandeep S. Dave
Keyword(s):  
Acute Myeloid Leukemia ◽  
Young Adults ◽  
Signaling Pathways ◽  
Myeloid Leukemia ◽  
Cox Proportional Hazards ◽  
Psychosocial Treatment ◽  
P Value ◽  
Related Factors ◽  
Disease Biology ◽  
Acute Myeloid

7107 Background: Adolescent and young adults (AYAs) with Acute Myeloid Leukemia (AML) have been shown to have better outcomes with induction chemotherapy when compared to older young adults (OYAs). Multiple psychosocial, treatment, and host-related factors unique to AYAs have been identified but the contribution of disease biology to these outcomes has not yet been fully characterized. The purpose of this study was to evaluate disease biology as it relates to age-specific differences in outcomes for AYAs with AML. Methods: Clinically annotated, microarray data from 425 patients with newly diagnosed AML from two publicly available datasets: GSE1159; and GSE12417 were analyzed. Age-specific cohorts (AYAs ≤ 30 years; n = 58 and OYAs >30 but ≤ 60 years; n=276) were prospectively identified. Patients in GSE1159 were treated according to protocols of the Dutch–Belgian Hematology–Oncology Cooperative group and included 111 patients who ultimately underwent stem-cell transplantation. Patients in GSE12417 were treated per the AMLCG-1999 protocol. Gene expression analysis was conducted by applying previously defined and tested signature profiles reflecting deregulation of oncogenic signaling pathways and altered tumor environment. All statistical analysis was performed using S-plus and survival analysis by Cox proportional-hazards regression was used to assess differences in overall survival (OS) between age-specified study cohorts and a one-sided p-value ≤ 0.05 was considered statistically significant. Results: AYA patients had a significantly better OS (median survival 24.1 months vs. 13.0 months in OYAs; p=0.0285), but there was no difference in Event Free Survival (p=0.23). Analysis of oncogenic pathways revealed that AYA patients likely had better OS because of lower TNF (p=0.03) and higher myc (p=0.02) pathway activation. Conclusions: AML arising in AYAs may represent a distinct biologic entity characterized by unique patterns of deregulated signaling pathways that contributes to OS. We hope these findings will enable clinically meaningful adjustments of treatment strategies in the AYA AML patient population.

scholarly journals Interaction between Mitochondria and the Actin Cytoskeleton in Budding Yeast Requires Two Integral Mitochondrial Outer Membrane Proteins, Mmm1p and Mdm10p

1998 ◽  
Vol 141 (6) ◽  
pp. 1371-1381 ◽  
Author(s):  
Istvan Boldogh ◽  
Nikola Vojtov ◽  
Sharon Karmon ◽  
Liza A. Pon
Keyword(s):  
Membrane Proteins ◽  
Actin Cytoskeleton ◽  
Outer Membrane ◽  
Outer Membrane Proteins ◽  
Protein S ◽  
Binding Activity ◽  
Actin Binding ◽  
Mitochondrial Outer Membrane ◽  
Mitochondrial Movement ◽  
Mitochondrial Motility

Transfer of mitochondria to daughter cells during yeast cell division is essential for viable progeny. The actin cytoskeleton is required for this process, potentially as a track to direct mitochondrial movement into the bud. Sedimentation assays reveal two different components required for mitochondria–actin interactions: (1) mitochondrial actin binding protein(s) (mABP), a peripheral mitochondrial outer membrane protein(s) with ATP-sensitive actin binding activity, and (2) a salt-inextractable, presumably integral, membrane protein(s) required for docking of mABP on the organelle. mABP activity is abolished by treatment of mitochondria with high salt. Addition of either the salt-extracted mitochondrial peripheral membrane proteins (SE), or a protein fraction with ATP-sensitive actin-binding activity isolated from SE, to salt-washed mitochondria restores this activity. mABP docking activity is saturable, resistant to high salt, and inhibited by pre-treatment of salt-washed mitochondria with papain. Two integral mitochondrial outer membrane proteins, Mmm1p (Burgess, S.M., M. Delannoy, and R.E. Jensen. 1994. J.Cell Biol. 126:1375–1391) and Mdm10p, (Sogo, L.F., and M.P. Yaffe. 1994. J.Cell Biol. 126:1361– 1373) are required for these actin–mitochondria interactions. Mitochondria isolated from an mmm1-1 temperature-sensitive mutant or from an mdm10 deletion mutant show no mABP activity and no mABP docking activity. Consistent with this, mitochondrial motility in vivo in mmm1-1 and mdm10Δ mutants appears to be actin independent. Depolymerization of F-actin using latrunculin-A results in loss of long-distance, linear movement and a fivefold decrease in the velocity of mitochondrial movement. Mitochondrial motility in mmm1-1 and mdm10Δ mutants is indistinguishable from that in latrunculin-A–treated wild-type cells. We propose that Mmm1p and Mdm10p are required for docking of mABP on the surface of yeast mitochondria and coupling the organelle to the actin cytoskeleton.

scholarly journals β2-adrenoceptor Activation Stimulates IL-6 Production via PKA, ERK1/2, Src, and Beta-arrestin2 Signaling Pathways in Human Bronchial Epithelia

2021 ◽  
Author(s):  
Rui Gang Zhang ◽  
Ya Niu ◽  
Ke Wu Pan ◽  
Hao Pang ◽  
Chung Ling Chen ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
Specific Inhibitor ◽  
Intracellular Camp ◽  
Cytokine Release ◽  
High Concentration ◽  
Airway Epithelia ◽  
Bronchial Epithelia ◽  
Adrenoceptor Agonists ◽  
Camp Receptor

Abstract Background: β 2 -adrenoceptor agonists are widely used to treat asthma because of their bronchial-dilation effects. However, a recent study describing a side effect of aggravating eosinophilic inflammation in the mouse airway epithelia by β 2 -adrenoceptor agonists could impact the future clinical use of these bronchodilators. We previously reported that isoprenaline, via the apical and basolateral β 2 -adrenoceptor, induced Cl - secretion by activating cyclic AMP (cAMP)-dependent pathways in human bronchial epithelia. Despite these results, whether and how the β 2 -adrenoceptor-mediated cAMP-dependent pathway contributes to pro-inflammatory cytokine release in human bronchial epithelia remains poorly understood.Methods: We investigated β 2 -adrenoceptor-mediated signaling pathways involved in the production of two pro-inflammatory cytokines, interleukin (IL)-6 and IL-8, in 16HBE14o- human bronchial epithelia. The effects of isoprenaline or formoterol were assessed in the presence of protein kinase A (PKA), exchange protein directly activated by cAMP (EPAC), Src, and extracellular signal-regulated protein kinase (ERK)1/2 inhibitors. The involvement of b-arrestin2 was examined using siRNA knockdown. Results: Both isoprenaline and formoterol (both β 2 agonists) induced IL-6, but not IL-8, release, which could be inhibited by ICI 118551 (β 2 antagonist). The PKA-specific inhibitor, H89, partially inhibited IL-6 release. Another intracellular cAMP receptor, EPAC, was not involved in IL-6 release. Isoprenaline-mediated IL-6 secretion was attenuated by dasatinib, a Src inhibitor, and PD98059, an ERK1/2 inhibitor. Isoprenaline treatment also led to ERK1/2 phosphorylation. In addition, knockdown of β-arrestin2 by siRNA specifically suppressed cytokine release when a high concentration of isoprenaline (1 mM) was used. Conclusion: Our results suggest that activation of the β 2 -adrenoceptor in 16HBE14o- cells stimulated the PKA/Src/ERK1/2 and/or β-arrestin2 signaling pathways, leading to IL-6 release. Therefore, our data reveal that β 2 -adrenoceptor signaling plays a role in the immune regulation of human airway epithelia.

Biochars prepared from rabbit manure for the adsorption of rhodamine B and Congo red: characterisation, kinetics, isotherms and thermodynamic studies

2020 ◽  
Vol 81 (3) ◽  
pp. 436-444
Author(s):  
Wen Huang ◽  
Min Zhang ◽  
Yinhai Wang ◽  
Jiao Chen ◽  
Jianqiang Zhang
Keyword(s):  
Rhodamine B ◽  
Congo Red ◽  
Molecular Layer ◽  
Suitable Model ◽  
Related Factors ◽  
Adsorption Sites ◽  
Rate Limiting Step ◽  
Layer Adsorption ◽  
Pseudo Second Order ◽  
Rate Limiting

Abstract Biochar was prepared from rabbit faeces (RFB550) at 550 °C through pyrolysis and was characterised using elemental analysis, scanning electron microscopy, Brunauer–Emmett–Teller analysis and Fourier transform infrared spectroscopy (FTIR). The related factors, kinetics, isothermal curves and thermodynamics of the adsorption behaviours were investigated by conducting batch experiments. The results revealed the adsorption equilibrium of rhodamine B (RhB) and Congo red (CR) onto RFB550 with initial concentrations of 30 mg · L−1 at 25 °C and 210 min, and the best adsorption was observed when the pH of the RhB and CR solutions was 3 and 5, respectively. Pseudo-second-order kinetics was the most suitable model for describing the adsorption of RhB and CR onto RFB550, indicating that the rate-limiting step was mainly chemical adsorption. The isotherm data were best described by the Freundlich model, and the adsorption process was multi-molecular layer adsorption. Thermodynamic parameters revealed the spontaneous adsorption of RhB and CR onto RFB550. According to the results of the FTIR analysis, the oxygen-containing functional groups and aromatic structures on the surface of RFB550 provided abundant adsorption sites for RhB and CR, and the adsorption mechanism was potentially related to the hydrogen bonds and π–π bonds.

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