Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0847097 (
acidity
)
15,165
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Background:
Cancer cells proliferate rapidly and are resistant to cell death, relying on aggravated glycolysis to satisfy their increased demand for energy and biosynthetic precursors. However, this process may create unfavorable microenvironments, such as increased
acidity
, leading to cytotoxicity. Our previous study demonstrated that arecoline induces anoikis of HA22T/VGH hepatoma cells. The present study aimed to examine if arecoline induced anoikis is related to the glycolytic pathway and explore the underlying mechanisms.
Methods:
HA22T/VGH cells were treated with arecoline and changes in the glycolytic end products lactate and ATP, glycolytic-related gene expression, intracellular and extracellular pH, pH-regulating gene expression, reactive oxygen species (ROS) levels, intracellular Ca
2+
concentration ([Ca
2+
]i) and mitochondrial membrane potential were examined, relative to untreated cells. Cell viability and morphology were also assessed.
Results:
Arecoline increased lactate and ATP production through induction of glycolytic genes, including glucose transporter 3 (Glut3), hexokinase 1 (HK1),
hexokinase 2
(
HK2
), and pyruvate kinase (PK). The intracellular pH was not changed, despite increased lactate levels, implying that intracellular H
+
was exported out of the cells. mRNA expression of pH regulators including monocarboxylate transporter 1 and 4 (MCT 1 and 4), sodium bicarbonate cotransporter 1 (NBC1), carbonic anhydrases (CA) IX and XII and vacuolar ATPase (V-ATPase) were down-regulated. Na
+
/H
+
exchanger 1 (NHE1) mRNA levels remained unchanged while Na
+
/Ca
2+
exchanger (NCX) was up-regulated and eventually [Ca
2+
]i was increased. ROS generation was increased and mitochondrial membrane potential was decreased followed by cell detachment and death. Addition of 2-deoxy-d-glucose, a glucose competitor that interferes with glycolysis, attenuated arecoline induction of lactate [Ca
2+
]i, ROS and cell detachment. Similarly, ROS scavengers could block the effects of arecoline.
Conclusions:
This study demonstrated that arecoline induced glycolysis and modulated the mRNA expression of pH-regulator genes in HA22T/VGH cells. This phenomenon led to the elevation of [Ca
2+
]i, ROS generation, and subsequent cell detachment.
...
PMID:Arecoline Increases Glycolysis and Modulates pH Regulator Expression in HA22T/VGH Hepatoma Cells, Leading to Increase of Intracellular Ca
2+
, Reactive Oxygen Species, and Anoikis. 2915 89
The properties of durian fruit at five stages of ripeness were evaluated and compared. The physicochemical parameters such as titratable
acidity
(TA) and total soluble solids (TSS) increased, whereas the pH slightly decreased during the ripening process. The highest contents of polyphenols, flavonoids, flavanols, tannins, vitamin C and the antioxidant capacities, measured by radical scavenging assays, were found in ripe and overripe fruits. The structural properties of extracted polyphenols were evaluated by Fourier transform infrared spectroscopy (FTIR) and fluorescence spectroscopy. The interaction of polyphenols with the main drug carrier in blood human serum albumin (HSA) showed decrease in its fluorescence intensity. The binding properties of polyphenols were in direct correlation with the antioxidant capacities of the investigated fruits. HepG2 cells evaluated cytotoxic effect and the mechanism of cell death after treatment with durian. The metabolism of carbohydrates was examined on the expression of glycolysis-related genes (
hexokinase 2
(
HK2
); 6-phosphofructo-2-kinase 4 (PFKFB4); facilitated glucose transporter member 1 (SLC2A1 (Glut1)) and lactate dehydrogenase A and utilization of glucose in the hepatocytes with durian treatment. Durian in immature stage had stronger cytotoxic effect and weak proapoptotic potential on HepG2 cells than the mature and overripe ones. The ripe and overripe fruits increased the expression of hepatic
HK2
and PFKFB4 glycolytic genes and stimulated glucose utilization in HepG2 cells. The present results indicate that durians reveal different biological activity and may provide their broad and extensive use as medicinal or functional foods.
...
PMID:Glycolytic genes expression, proapoptotic potential in relation to the total content of bioactive compounds in durian fruits. 3155 73
