Biology subjects

Ismail, I.

Publications and source records attributed to Ismail, I..

3 recordsLinked to original sources

bioRxiv2023

DIURETIC AND ANTI-HYPERTENSIVE ACTIVITY OF CLERODENDRUM CHINENSE (OSBECK) MABB. AQUEOUS EXTRACT IN 8% SALT DIET INDUCED HYPERTENSIVE RATS.

Diuresis refers to increase in the rate of urine flow and sodium excretion from the system via the urine. It is a necessary excretory process that may prove difficult for some disease systems e.g. enlarged prostates. Hypertension occurs as a result of systolic blood pressure higher than 140 mmHg or a diastolic blood pressure higher than 90 mmHg. It is one of the most common chronic diseases affecting more a billion people worldwide. A high dietary sodium intake is one of the factors associated with the development of hypertension. Clerodendrum chinensis is used by local communities in West Africa for its diuretic and anti-hypertensive properties. We analyse the phytochemical properties of the mixed leaf, root and stem aqueous extract of the plant and investigate its anti-hypertensive and diuretic activity in Sodium chloride diet induced hypertensive rats. The anti-hypertensive effect of extract at different concentrations (100, 200 and 300 mg/kg) was studied and compared with known drug compound; Furosemide. Treated animal urine was analyzed for urinary excretion and diuretic action. The anti-hypertensive effect was statistically significant when compared with the control p < 0.001. The extract at 100mg/kg demonstrated the best systolic and diastolic blood pressure lowering potential as compared to other concentrations. The diuretic action of the plant extract at the lowest dose (100 mg/kg) was high and quantitatively similar to the standard drug. The combined powdered leaf, stem and roots aqueous extract of C. chinense possesses anti-hypertensive and diuretic potential in salt loaded hypertensive rats.

pharmacology and toxicology↗

bioRxiv2023

Polyphosphate uses mTOR, pyrophosphate, and Rho GTPase components to potentiate bacterial survival in Dictyostelium

Human macrophages and the eukaryotic microbe Dictyostelium discoideum ingest bacteria by phagocytosis, and then kill the ingested bacteria. Some pathogenic bacteria secrete linear chains of phosphate residues (polyphosphate; polyP), and the polyP causes the phagocytes to not kill the ingested bacteria. In D. discoideum, the effect of polyP requires the G protein-coupled receptor GrlD, suggesting that polyP uses a signal transduction pathway to inhibit killing of ingested bacteria. Here we show that in addition to GrlD, the D. discoideum polyP signaling pathway requires the GPCR interacting arrestin-like protein AdcB, inositol hexakisphosphate kinase A (I6kA), the Rho GTPase RacE, and the TOR component Lst8. D. discoideum also secretes polyP, and at high concentrations polyP inhibits D. discoideum cytokinesis. The polyP inhibition of bacterial killing pathway does not appear to involve many of the polyP inhibition of cytokinesis pathway components. These data suggest the intriguing possibility that if there is a similar polyP inhibition of bacterial killing pathway in macrophages, pharmacologically blocking this pathway could potentiate macrophage killing of pathogenic bacteria. ImportanceAlthough most bacteria are quickly killed after phagocytosis by a eukaryotic cell, some pathogenic bacteria prevent their killing after phagocytosis. Pathogenic Mycobacterium species secrete polyP, and the polyP is necessary for the bacteria to prevent their killing after phagocytosis. Conversely, exogenous polyP prevents the killing of ingested bacteria that are normally killed after phagocytosis by human macrophages and the eukaryotic microbe Dictyostelium discoideum. This suggests the possibility that in these cells, a signal transduction pathway is used to sense polyP and prevent killing of ingested bacteria. In this report, we identify key components of the polyP signal transduction pathway in D. discoideum. In cells lacking these components, polyP is unable to inhibit killing of ingested bacteria. The pathway components have orthologues in human cells, and an exciting possibility is that pharmacologically blocking this pathway in human macrophages would cause them to kill ingested pathogens such as M. tuberculosis.

microbiology↗

bioRxiv2023

Starvation induces extracellular accumulation of polyphosphate in Dictyostelium discoideum to inhibit macropinocytosis, phagocytosis, and exocytosis

Dictyostelium discoideum is a soil-dwelling unicellular eukaryote that accumulates extracellular polyphosphate (polyP). At high cell densities, when the cells are about to overgrow their food supply and starve, the corresponding high extracellular concentrations of polyP allow the cells to preemptively anticipate starvation, inhibit proliferation, and prime themselves to begin development. In this report, we show that starved D. discoideum cells accumulate cell surface and extracellular polyP. Starvation reduces macropinocytosis, exocytosis, and phagocytosis, and we find that these effects require the G protein-coupled polyP receptor (GrlD) and two enzymes, Polyphosphate kinase 1 (Ppk1), which is required for synthesizing intracellular polyP, cell surface polyP, and some of the extracellular polyP, and Inositol hexakisphosphate kinase (I6kA), which is required for cell surface polyP and polyP binding to cells, and some of the extracellular polyP. PolyP reduces membrane fluidity, and we find that starvation reduces membrane fluidity, and this effect requires GrlD and Ppk1 but not I6kA. Together, these data suggest that in starved cells, extracellular polyP decreases membrane fluidity, possibly as a protective measure. In the starved cells, sensing polyP appears to decrease energy expenditure from ingestion, and decrease exocytosis, to both decrease energy expenditures and retain nutrients.

cell biology↗