Dataset Information

Al-Husari2013 - pH and lactate in tumor

ABSTRACT: The paper describes a model of pH control in tumor. Created by COPASI 4.26 (Build 213) This model is described in the article: Regulation of tumour intracellular pH: A mathematical model examining the interplay between H and lactate Maymona Al-Husari, Steven D. Webb Journal of Theoretical Biology 322 (2013) 58–71 Abstract: Non-invasive measurements of pH have shown that both tumour and normal cells have intracellular pH (pHi) that lies on the alkaline side of neutrality (7.1–7.2). However, extracellular pH (pHe) is reported to be more acidic in some tumours compared to normal tissues. Many cellular processes and therapeutic agents are known to be tightly pH dependent which makes the study of intracellular pH regulation of paramount importance. We develop a mathematical model that examines the role of various membrane-based ion transporters in tumour pH regulation, in particular, with a focus on the interplay between lactate and H ions and whether the lactate/H symporter activity is sufficient to give rise to the observed reversed pH gradient that is seen is some tumours. Using linear stability analysis and H ions. We extend this analysis using perturbation techniques to specifically examine a rapid change in H-ion concentrations relative to variations in lactate. We then perform a parameter sensitivity analysis to explore solution robustness to parameter variations. An important result from our study is that a reversed pH gradient is possible in our system but for unrealistic parameter estimates—pointing to the possible involvement of other mechanisms in cellular pH gradient reversal, for example acidic vesicles, lysosomes, golgi and endosomes. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

SUBMITTER: Jinghao Men

PROVIDER: BIOMD0000000805 | BioModels | 2024-09-02

REPOSITORIES: BioModels

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	BIOMD0000000805?filename=Al-Husari2013.cps	Other
	BIOMD0000000805?filename=Al-Husari2013.sedml	Other
	BIOMD0000000805?filename=Al-Husari2013.xml	Xml

Items per page:

1 - 3 of 3

Publications

Regulation of tumour intracellular pH: a mathematical model examining the interplay between H+ and lactate.

Al-Husari Maymona M Webb Steven D SD

Journal of theoretical biology 20130120

Non-invasive measurements of pH have shown that both tumour and normal cells have intracellular pH (pHi) that lies on the alkaline side of neutrality (7.1-7.2). However, extracellular pH (pHe) is reported to be more acidic in some tumours compared to normal tissues. Many cellular processes and therapeutic agents are known to be tightly pH dependent which makes the study of intracellular pH regulation of paramount importance. We develop a mathematical model that examines the role of various membr ...[more]

PMID: 23340437

Similar Datasets

Project description:Aluminum (Al) is the most common metal in the Earth’s crust and Al toxicity is considered to be the most harmful abiotic stress in acidic soils that today comprise more than 50% of the world’s arable lands. The first symptom of Al toxicity is the reduction of root growth, resulting in decreased water and nutrients uptake, plant growth retardation, and finally, yield reduction. Barley (Hordeum vulgare L.), which is the fourth cereal crop in regards to cultivation area and production tonnage, belongs to crops most sensitive to toxic aluminum ions in low pH soils. We present the RNA-seq transcriptome analysis of root meristems of barley seedlings grown in hydroponics at optimal pH (6.0), low pH (4.0), and low pH with Al (10 µM of bioavailable Al3+ ions). Two independent experiments were conducted: with short-term (24 h) and long-term (7 days) Al treatment. Interestingly, in the short-term experiment, more genes were differentially expressed between root meristems grown at pH=6.0 and pH=4.0, than between those grown at pH=4.0 with and without Al treatment. The upregulated genes that were overrepresented at conditions of low pH, compared to optimal pH, were associated with response to oxidative stress, cell wall organization, and iron ion binding. Among genes downregulated by low pH were mainly those related to chromatin organization. These results show that low pH itself is a severe stress for barley plants. Among genes upregulated by short Al treatment, overrepresented were those related to response to stress condition and calcium ion binding. After 7 days of hydroponics, the number of DEGs between hydroponics at pH=4.0 and 6.0 were still high but lower than in the short-term experiment, which suggests that plants partially adapted to the low pH. Interestingly, 7 day Al treatment caused massive changes in the transcriptome profile compared to the condition of low pH alone. Over 4 000 genes were upregulated and almost 2 000 genes were downregulated by long-term Al stress. These DEGs were related to e.g. stress response, cell wall development and metal ion transport. Based on our results we can assume that both, Al3+ ions and low pH are harmful to barley plants.Additionally, we phenotyped in detail the root system of barley seedlings grown in the same hydroponic conditions for 7 days at pH=6.0, pH=4.0, and pH=4.0 with Al. The results correspond to transcriptomic data and show that low pH itself is a stress facor that causes a significant reduction of root growth and the addition of aluminum further increases this reduction. It should be underlined that in the acidic arable lands, plants are exposed simultaneously to both of these stresses (low pH and Al), as Al becomes soluble at pH below 5.5. The presented transcriptome analysis may help to find potential targets for breeding barley plants more tolerant to such conditions.