bims-prodis 2018-09-16 papers

Issue of 2018–09–16
four papers selected by
Nancy Gough, Bioserendipity

Trends Parasitol. 2018 Sep 05. pii: S1471-4922(18)30174-0. [Epub ahead of print]

Proteomics of Anopheles Vectors of Malaria.

Proteomic investigations in Anopheles gained momentum following the sequencing of the Anopheles gambiae genome, allowing peptide data from mass spectrometry to be searched against large datasets of predicted protein sequences. Exhaustive discovery proteomics investigations have improved the annotation of genomic datasets and catalogued proteins from mosquito tissues, including the salivary glands, midgut, and sensory appendages. These efforts have revealed protein constituents that define the unique biological functions of these organs. Quantitative proteomics investigations have begun to characterise the molecular basis of mosquito behaviour and immune responses. With a current trend towards increasing sensitivity of mass spectrometers and simpler workflows, proteomics is set to accelerate the development of antiparasite interventions through the identification of new targets for parasite or vector control and diagnostic biomarkers.

Keywords: Anopheles; mass spectrometry; mosquito vectors; proteome; tissue analysis

DOI: https://doi.org/10.1016/j.pt.2018.08.009

Phytomedicine. 2018 Sep 15. pii: S0944-7113(18)30181-8. [Epub ahead of print]48 179-186

Nitensidine B affects proteins of the glycolytic pathway and induces apoptosis in cervical carcinoma cells immortalized by HPV16.

Felipe de Oliveira Souza, Juliana Maria Sorbo, Luís Octávio Regasini, Vanderlan da Silva Bolzani, José César Rosa, Érica da Silva Czernys, Valéria Valente, Thaís Fernanda Moreira, Geovana Navegante, Barbara Colatto Fernandes, Christiane Pienna Soares.

BACKGROUND: Cervical cancer, the fourth most common type of cancer among women worldwide, accounts for approximately 12% of all types of malignancies that affect women. Natural products have contributed significantly to the development of modern therapies; approximately 70% of the drugs available for chemotherapy are naturally based products.
PURPOSE: The purpose of this study was to examine the biological activities of nitensidine B (NTB), a guanidinic alkaloid isolated from the leaves of Pterogyne nitens Tul. (Fabaceae) in a cervical cancer cell line.
METHODS: In vitro experiments were performed using cervical carcinoma cells immortalized by human papillomavirus type 16 (HPV16, SiHa cells), since epidemiological and molecular studies have demonstrated robust associations between the etiologies of cervical cancer and HPV infection. Cytotoxicity as well as the effect of NTB treatment on intracellular signals of apoptosis, fragmentation of internucleosomal DNA via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and levels of apoptosis effectors (Caspase 3/7) were evaluated. In addition, differential proteomic analysis (iTRAQ) and protein validation using western blot were performed.
RESULTS: The cytotoxicity of NTB treatment in the SiHa cell line was concentration-dependent, with the minimum inhibitory concentration of 50% of the cells of 40.98 µM. In the TUNEL assay, SiHa cell apoptosis with 3/7 caspase activation was reported at 12 h following treatment. Differential proteomic analysis by iTRAQ demonstrated that proteins of the glycolytic pathway, aldolase A, alpha-enolase, pyruvate kinase, and glyceraldehyde 3-phosphate dehydrogenase were underexpressed.
CONCLUSION: These results indicated that NTB could play a role in decreasing glycolysis . Since tumor cells prefer the glycolytic pathway to generate energy, these findings suggest that NTB may be a reliable model for the study of human cervical cancer cell lines immortalized by HPV16, however more experiments can be performed.

Keywords: Apoptosis; Cervical cancer; Glycolytic pathway; Nitensidine B; Proteomic analysis

DOI: https://doi.org/10.1016/j.phymed.2018.05.016

Prog Neuropsychopharmacol Biol Psychiatry. 2018 Sep 05. pii: S0278-5846(18)30439-1. [Epub ahead of print]

Link between depression and cardiovascular diseases due to epigenomics and proteomics: Focus on energy metabolism.

Kai G Kahl, Britta Stapel, Helge Frieling.

Keywords: Cardiovascular diseases; Energy metabolism; Epigenomics; Major depression; Proteomics

DOI: https://doi.org/10.1016/j.pnpbp.2018.09.004

Mol Ther Nucleic Acids. 2018 Sep 07. pii: S2162-2531(18)30067-2. [Epub ahead of print]12 45-56

RNA Aptamers Rescue Mitochondrial Dysfunction in a Yeast Model of Huntington's Disease.

Kinjal A Patel, Rajeev K Chaudhary, Ipsita Roy.

Huntington's disease (HD) is associated with the misfolding and aggregation of mutant huntingtin harboring an elongated polyglutamine stretch at its N terminus. A distinguishing pathological hallmark of HD is mitochondrial dysfunction. Any strategy that can restore the integrity of the mitochondrial environment should have beneficial consequences for the disease. Specific RNA aptamers were selected that were able to inhibit aggregation of elongated polyglutamine stretch containing mutant huntingtin fragment (103Q-htt). They were successful in reducing the calcium overload, which leads to mitochondrial membrane depolarization in case of HD. In one case, the level of Ca2+ was restored to the level of cells not expressing 103Q-htt, suggesting complete recovery. The presence of aptamers was able to increase mitochondrial mass in cells expressing 103Q-htt, along with rescuing loss of mitochondrial genome. The oxidative damage to the proteome was prevented, which led to increased viability of cells, as monitored by flow cytometry. Thus, the presence of aptamers was able to inhibit aggregation of mutant huntingtin fragment and restore mitochondrial dysfunction in the HD cell model, confirming the advantage of the strategy in a disease-relevant parameter.

Keywords: calcium homeostasis; intramers; membrane depolarization; mitochondrial mass; oxidative damage; reactive oxygen species

DOI: https://doi.org/10.1016/j.omtn.2018.04.010