Identification and Functional Characterization of Bax-binding Pharmacophores Capable of Inhibiting Cell Death in Culture Neurons by Blocking Protein Bax

Background: (1-(2-hydroxy-5-nitrophenyl)(4-hydroxyphenyl)methyl)indoline-4-carbonitrile (HIC), an agonist of the P2Y1 receptor (P2Y1R), induces cell death in prostate cancer cells. However, the molecular mechanism behind the inhibition of HIC in prostate cancer remains elusive. Methods and results: Here, to outline the inhibitory role of HIC on prostate cancer cells, PC-3 and DU145 cell lines were treated with the respective IC50 concentrations, which reduced cell proliferation, adherence properties and spheroid formation. HIC was able to arrest the cell cycle at G1/S phase and also induced apoptosis and DNA damage, validated by gene expression profiling. HIC inhibited the prostate cancer cells’ migration and invasion, revealing its antimetastatic ability. P2Y1R-targeted HIC affects p53, MAPK and NF-κB protein expression, thereby improving the p53 stabilization essential for G1/S arrest and cell death. Conclusion: These findings provide an insight on the potential use of HIC, which remains the mainstay treatment for prostate cancer.

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Functional Characterization of the Nep1-Like Protein Effectors of the Necrotrophic Pathogen – Alternaria brassicae

Frontiers in Microbiology ◽

10.3389/fmicb.2021.738617 ◽

2021 ◽

Vol 12 ◽

Author(s):

Deepak Duhan ◽

Shivani Gajbhiye ◽

Rajdeep Jaswal ◽

Ravindra Pal Singh ◽

Tilak Raj Sharma ◽

...

Keyword(s):

Cell Death ◽

Host Species ◽

Functional Characterization ◽

Subcellular Location ◽

Ethylene Biosynthesis ◽

Alternaria Brassicae ◽

Necrotrophic Pathogen ◽

Molecular Pattern ◽

Pathogen Associated Molecular Pattern

Alternaria brassicae is an important necrotrophic pathogen that infects the Brassicaceae family. A. brassicae, like other necrotrophs, also secretes various proteinaceous effectors and metabolites that cause cell death to establish itself in the host. However, there has been no systematic study of A. brassicae effectors and their roles in pathogenesis. The availability of the genome sequence of A. brassicae in public domain has enabled the search for effectors and their functional characterization. Nep1-like proteins (NLPs) are a superfamily of proteins that induce necrosis and ethylene biosynthesis. They have been reported from a variety of microbes including bacteria, fungi, and oomycetes. In this study, we identified two NLPs from A. brassicae viz. AbrNLP1 and AbrNLP2 and functionally characterized them. Although both AbrNLPs were found to be secretory in nature, they localized differentially inside the plant. AbrNLP2 was found to induce necrosis in both host and non-host species, while AbrNLP1 could not induce necrosis in both species. Additionally, AbrNLP2 was shown to induce pathogen-associated molecular pattern (PAMP)-triggered immunity in both host and non-host species. Overall, our study indicates that AbrNLPs are functionally and spatially (subcellular location) distinct and may play different but important roles during the pathogenesis of A. brassicae.

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Functional characterization of calliphorid cell death genes and cellularization gene promoters for controlling gene expression and cell viability in early embryos

Insect Molecular Biology ◽

10.1111/imb.12135 ◽

2014 ◽

Vol 24 (1) ◽

pp. 58-70 ◽

Cited By ~ 10

Author(s):

R. M. Edman ◽

R. J. Linger ◽

E. J. Belikoff ◽

F. Li ◽

S.-H. Sze ◽

...

Keyword(s):

Gene Expression ◽

Cell Death ◽

Cell Viability ◽

Functional Characterization ◽

Gene Promoters ◽

Early Embryos ◽

Cell Death Genes ◽

Death Genes

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Functional characterization of human brown adipose tissue metabolism

Biochemical Journal ◽

10.1042/bcj20190464 ◽

2020 ◽

Vol 477 (7) ◽

pp. 1261-1286 ◽

Cited By ~ 3

Author(s):

Marie Anne Richard ◽

Hannah Pallubinsky ◽

Denis P. Blondin

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Functional Characterization ◽

Human Infants ◽

Positron Emission ◽

Brown Adipose ◽

Treatment Of Obesity ◽

And Function

Brown adipose tissue (BAT) has long been described according to its histological features as a multilocular, lipid-containing tissue, light brown in color, that is also responsive to the cold and found especially in hibernating mammals and human infants. Its presence in both hibernators and human infants, combined with its function as a heat-generating organ, raised many questions about its role in humans. Early characterizations of the tissue in humans focused on its progressive atrophy with age and its apparent importance for cold-exposed workers. However, the use of positron emission tomography (PET) with the glucose tracer [18F]fluorodeoxyglucose ([18F]FDG) made it possible to begin characterizing the possible function of BAT in adult humans, and whether it could play a role in the prevention or treatment of obesity and type 2 diabetes (T2D). This review focuses on the in vivo functional characterization of human BAT, the methodological approaches applied to examine these features and addresses critical gaps that remain in moving the field forward. Specifically, we describe the anatomical and biomolecular features of human BAT, the modalities and applications of non-invasive tools such as PET and magnetic resonance imaging coupled with spectroscopy (MRI/MRS) to study BAT morphology and function in vivo, and finally describe the functional characteristics of human BAT that have only been possible through the development and application of such tools.

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