Mevalonosomes: specific vacuoles containing the mevalonate pathway in Plocamium brasiliense cortical cells (Rhodophyta)

2015 ◽  
Vol 51 (2) ◽  
pp. 225-235 ◽  
Author(s):  
Wladimir Costa Paradas ◽  
Thalita Mendes Crespo ◽  
Leonardo Tavares Salgado ◽  
Leonardo Rodrigues de Andrade ◽  
Angélica Ribeiro Soares ◽  
...  
Author(s):  
T. M. Murad ◽  
Karen Israel ◽  
Jack C. Geer

Adrenal steroids are normally synthesized from acetyl coenzyme A via cholesterol. Cholesterol is also shown to enter the adrenal gland and to be localized in the lipid droplets of the adrenal cortical cells. Both pregnenolone and progesterone act as intermediates in the conversion of cholesterol into steroid hormones. During pregnancy an increased level of plasma cholesterol is known to be associated with an increase of the adrenal corticoid and progesterone. The present study is designed to demonstrate whether the adrenal cortical cells show any dynamic changes during pregnancy.


1974 ◽  
Vol 76 (4) ◽  
pp. 729-740 ◽  
Author(s):  
Peter Kamp ◽  
Per Platz ◽  
Jørn Nerup

ABSTRACT By means of an indirect immunofluorescence technique, sera from 116 patients with Addison's disease, an equal number of age and sex matched controls and 97 patients with other endocrine diseases were examined for the occurrence of antibody to steroid-producing cells in ovary, testis and adrenal cortex. Fluorescent staining was observed in the theca cells of growing follicles, the theca lutein cells, testicular Leydig cells and adrenal cortical cells, i. e. cells which contain enzyme systems used in steroid hormone production. The "steroid-cell" antibody was present in 24 % of the patients with idiopathic Addison's disease, equally frequent in males and females, and in 17 % of the patients with tuberculous Addison's disease, but was rarely found in controls, including patients with other endocrine diseases. Female hypergonadotrophic hypogonadism made an exception, since the "steroid-cell" antibody was found in about half the cases with this condition.


Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 2076-P
Author(s):  
ALICE MURPHY ◽  
SAHAR AZHARIAN ◽  
GYANENDRA TRIPATHI ◽  
GUY BARKER ◽  
MICHAEL J. CHAPPELL ◽  
...  

2019 ◽  
Author(s):  
Patrick R. A. Zanon ◽  
Lisa Lewald ◽  
Stephan M. Hacker

Rapid development of bacterial resistance has led to an urgent need to find new druggable targets for antibiotics. In this context, residue-specific chemoproteomic approaches enable proteome-wide identification of binding sites for covalent inhibitors. Here, we describe isotopically labeled desthiobiotin azide (isoDTB) tags that are easily synthesized, shorten the chemoproteomic workflow and allow an increased coverage of cysteines in bacterial systems. We quantify 59% of all cysteines in essential proteins in <i>Staphylococcus aureus</i> and discover 88 cysteines with high reactivity, which correlates with functional importance. Furthermore, we identify 268 cysteines that are engaged by covalent ligands. We verify inhibition of HMG-CoA synthase, which will allow addressing the bacterial mevalonate pathway through a new target. Overall, a comprehensive map of the bacterial cysteinome is obtained, which will facilitate the development of antibiotics with novel modes-of-action.


2020 ◽  
Vol 17 (5) ◽  
pp. 616-618
Author(s):  
Kimia Kazemi ◽  
Negin Mozafari ◽  
Hajar Ashrafi ◽  
Pedram Rafiei ◽  
Amir Azadi

Background: Non-Hodgkin's lymphomas (NHL), derived from B- or T-cell, consist of a heterogeneous group of malignant lymphoproliferative disorders. Knockdown of Casein kinase 2 interacting protein-1 (CKIP-1) in NHL promoted cell proliferation and inhibited apoptosis via enhancing phosphorylated Protein Kinase B (PKB or AKT) expression. Statins are the class of drugs that inhibit the ratelimiting step of the mevalonate pathway, which is essential for the biosynthesis of various compounds, including cholesterol. Also, statins have anticancer properties being mediated by different mechanisms. Methods: A search on databases like Scopus and PubMed with keywords such as statin and non- Hodgkin's lymphomas was performed and Kyoto Encyclopedia of Genes and Genomes (KEGG) website was used to evaluate and reconfirm the involved cellular signaling pathway. Results: CKIP-1 is involved in the regulation of cell proliferation and apoptosis while plays an important role in many cancers. We can hypothesize that statins may increase the expression levels of CKIP-1 which could contribute to the reductions in phospho-AKT level. Hence, they may ameliorate the NHL patients via suppressing AKT phosphorylation and increasing CKIP- expression. Conclusion: Present review confirms the positive effect of statins on NHL by increasing CKIP-1 and reducing cell proliferation, subsequently.


2019 ◽  
Vol 15 (2) ◽  
pp. 131-145
Author(s):  
Gajanan V. Sherbet

The mevalonate pathway (also known as the cholesterol biosynthesis pathway) plays a crucial metabolic role in normal cell function as well as in the pathological environment. It leads to the synthesis of sterol and non-sterol isoprenoid biomolecules which subserve a variety of cellular functions. It is known to be deregulated in many disease processes. Statins and bisphosphonates are prominent inhibitors of the mevalonate pathway. They inhibit cell proliferation and activate apoptotic signalling and suppress tumour growth. Statins subdue metastatic spread of tumours by virtue of their ability to suppress invasion and angiogenesis. The induction of autophagy is another feature of statin effects that could contribute to the suppression of metastasis. Herein highlighted are the major signalling systems that statins engage to generate these biological effects. Statins can constrain tumour growth by influencing the expression and function of growth factor and receptor systems. They may suppress epithelial mesenchymal transition with resultant inhibition of cell survival signalling, together with the inhibition of cancer stem cell generation, and their maintenance and expansion. They can suppress ER (oestrogen receptor)-α in breast cancer cells. Statins have been implicated in the activation of the serine/threonine protein kinase AMPK (5&#039; adenosine monophosphate-activated protein) leading to the suppression of cell proliferation. Both statins and bisphosphonates can suppress angiogenic signalling by HIF (hypoxia- inducible factor)-1/eNOS (endothelial nitric oxide synthase) and VEGF (vascular endothelial growth factor)/VEGFR (VEGF receptor). Statins have been linked with improvements in disease prognosis. Also attributed to them is the ability of cancer prevention and reduction of risk of some forms of cancer. The wide spectrum of cancer associated events which these mevalonate inhibitors appear to influence would suggest a conceivable role for them in cancer management. However, much deliberation is warranted in the design and planning of clinical trials, their scope and definition of endpoints, modes risk assessment and the accrual of benefits.


1977 ◽  
Vol 25 (5) ◽  
pp. 483 ◽  
Author(s):  
N Malajczuk ◽  
AJ Mccomb ◽  
CA Parker

On lateritic podzolic soils in Western Australia Eucalyptus calophylla is resistant to Phytophthora cinnamomi whereas Eucalyptus marginata is susceptible and eventually killed by the pathogen. On loam soils both eucalypts are resistant. Possible mechanisms for resistance of E. calophylla in lateritic soil and the inhibitory action of loam soils were investigated. Aseptically raised eucalypt seedlings succumbed to infection in liquid culture tubes. The mechanism of infection was compared by light and electron microscopy which showed similar fungal invasion and penetration into roots of both eucalypt species. Vegetative hyphae initially penetrated intercellularly and proliferated rapidly within cortical and stelar tissue. Intracellular invasion of these tissues occurred 48hr after initial infection through dissolution of the host cell wall. Chlamydospores were formed within a number of cortical cells. Unsuberized roots of mature trees produced aseptically showed reactions to invasion similar to those of the eucalypt seedling roots. Suberized roots were not invaded. The addition of small quantities of lateritic soil to sterile sand so as to introduce soil micro-organisms without altering the chemical and physical status of the sand, and subsequent inoculation of the sand with P.cinnamomi, resulted in a reduction of root damage on both eucalypts when compared with seedlings raised in sterile sand. Roots of E.calophylla were less severely damaged than those of E.marginata. The addition of small quantities of loam soil significantly reduced root damage in seedlings of both species. These results parallel both pot experiments and field observations, and suggest that microorganisms of the rhizosphere may be an important factor in the resistance of E.calophylla to infection, and in the inhibitory effect of loam soil on P.cinnamomi.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
James Kirby ◽  
Gina M. Geiselman ◽  
Junko Yaegashi ◽  
Joonhoon Kim ◽  
Xun Zhuang ◽  
...  

Abstract Background Mitigation of climate change requires that new routes for the production of fuels and chemicals be as oil-independent as possible. The microbial conversion of lignocellulosic feedstocks into terpene-based biofuels and bioproducts represents one such route. This work builds upon previous demonstrations that the single-celled carotenogenic basidiomycete, Rhodosporidium toruloides, is a promising host for the production of terpenes from lignocellulosic hydrolysates. Results This study focuses on the optimization of production of the monoterpene 1,8-cineole and the sesquiterpene α-bisabolene in R. toruloides. The α-bisabolene titer attained in R. toruloides was found to be proportional to the copy number of the bisabolene synthase (BIS) expression cassette, which in turn influenced the expression level of several native mevalonate pathway genes. The addition of more copies of BIS under a stronger promoter resulted in production of α-bisabolene at 2.2 g/L from lignocellulosic hydrolysate in a 2-L fermenter. Production of 1,8-cineole was found to be limited by availability of the precursor geranylgeranyl pyrophosphate (GPP) and expression of an appropriate GPP synthase increased the monoterpene titer fourfold to 143 mg/L at bench scale. Targeted mevalonate pathway metabolite analysis suggested that 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGR), mevalonate kinase (MK) and phosphomevalonate kinase (PMK) may be pathway bottlenecks are were therefore selected as targets for overexpression. Expression of HMGR, MK, and PMK orthologs and growth in an optimized lignocellulosic hydrolysate medium increased the 1,8-cineole titer an additional tenfold to 1.4 g/L. Expression of the same mevalonate pathway genes did not have as large an impact on α-bisabolene production, although the final titer was higher at 2.6 g/L. Furthermore, mevalonate pathway intermediates accumulated in the mevalonate-engineered strains, suggesting room for further improvement. Conclusions This work brings R. toruloides closer to being able to make industrially relevant quantities of terpene from lignocellulosic biomass.


Author(s):  
Dandan Wang ◽  
Brian W. Howell ◽  
Eric C. Olson

AbstractFetal alcohol syndrome (FAS) is characterized by disrupted fetal brain development and postnatal cognitive impairment. The targets of alcohol are diverse, and it is not clear whether there are common underlying molecular mechanisms producing these disruptions. Prior work established that acute ethanol exposure causes a transient increase in tyrosine phosphorylation of multiple proteins in cultured embryonic cortical cells. In this study, we show that a similar tyrosine phosphorylation transient occurs in the fetal brain after maternal dosing with ethanol. Using phospho-specific antibodies and immunohistochemistry, we mapped regions of highest tyrosine phosphorylation in the fetal cerebral cortex and found that areas of dendritic and axonal growth showed elevated tyrosine phosphorylation 10 min after maternal ethanol exposure. These were also areas of Src expression and Src family kinase (SFK) activation loop phosphorylation (pY416) expression. Importantly, maternal pretreatment with the SFK inhibitor dasatinib completely prevents both the pY416 increase and the tyrosine phosphorylation response. The phosphorylation response was observed in the perisomatic region and neurites of immature migrating and differentiating primary neurons. Importantly, the initial phosphotyrosine transient (~ 30 min) targets both Src and Dab1, two critical elements in Reelin signaling, a pathway required for normal cortical development. This initial phosphorylation response is followed by sustained reduction in Ser3 phosphorylation of n-cofilin, a critical actin severing protein and an identified downstream effector of Reelin signaling. This biochemical disruption is associated with sustained reduction of F-actin content and disrupted Golgi apparatus morphology in developing cortical neurons. The finding outlines a model in which the initial activation of SFKs by ethanol has the potential to disrupt multiple developmentally important signaling systems for several hours after maternal exposure.


Sign in / Sign up

Export Citation Format

Share Document