Increased aquaglyceroporin 9 expression disrupts arsenic resistance in human lung cancer cells

Miao, Zhi-Feng; Chang, Eddy Essen; Tsai, Feng-Yuan; Yeh, Szu-Ching; Wu, Kuen-Yuh; Wang, Chien-Jen; Tsou, Tsui‐Chun

doi:10.1016/j.tiv.2008.11.011

Cited by 20 publications

(15 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results are consistent with a role for AQP9 in arsenite export, which is in contrast to previous studies of cultured cells (7,(12)(13)(14)(15). However, our studies do not exclude a role for AQP9 in arsenite import.…”

Section: Discussionsupporting

confidence: 81%

“…Excretion of arsenic in urine and feces of AQP9-null mice is greatly reduced. Although AQP9 is known to facilitate uptake of arsenite by single cells in culture (12)(13)(14)(15), our studies cause us to propose that AQP9 also facilitates in vivo arsenic excretion by the liver, thereby providing partial protection against arsenic toxicity.…”

mentioning

confidence: 81%

“…The mammalian aquaglyceroporins AQP3, AQP7, and AQP9 were shown to transport arsenite and antimonite (7,11). Studies of multiple cultured cell lines revealed increased AQP3 or AQP9 expression, resulting in increased arsenic accumulation and toxicity (7,(12)(13)(14)(15). A human lung adenocarcinoma cell line resistant to arsenic was found to have decreased levels of AQP3 (7).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Reduced arsenic clearance and increased toxicity in aquaglyceroporin-9-null mice

Carbrey

Song

Zhou³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Expressed in liver, aquaglyceroporin-9 (AQP9) is permeated by glycerol, arsenite, and other small, neutral solutes. To evaluate a possible protective role, AQP9-null mice were evaluated for in vivo arsenic toxicity. After injection with NaAsO 2, AQP9-null mice suffer reduced survival rates (LD 50, 12 mg/kg) compared with WT mice (LD 50, 15 mg/kg). The highest tissue level of arsenic is in heart, with AQP9-null mice accumulating 10 -20 times more arsenic than WT mice. Within hours after NaAsO 2 injection, AQP9-null mice sustain profound bradycardia, despite normal serum electrolytes. Increased arsenic levels are also present in liver, lung, spleen, and testis of AQP9-null mice. Arsenic levels in the feces and urine of AQP9-null mice are only Ϸ10% of the WT levels, and reduced clearance of multiple arsenic species by the AQP9-null mice suggests that AQP9 is involved in the export of multiple forms of arsenic. Immunohistochemical staining of liver sections revealed that AQP9 is most abundant in basolateral membrane of hepatocytes adjacent to the sinusoids. AQP9 is not detected in heart or kidney by PCR or immunohistochemistry. We propose that AQP9 provides a route for excretion of arsenic by the liver, thereby providing partial protection of the whole animal from arsenic toxicity.

show abstract

Section: Discussionsupporting

confidence: 81%

mentioning

confidence: 81%

mentioning

confidence: 99%

See 1 more Smart Citation

Reduced arsenic clearance and increased toxicity in aquaglyceroporin-9-null mice

Carbrey

Song

Zhou³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Uptake of arsenite by hepatocytes via AQP9s [36] is governed by their electrochemical potential across the cellular membrane (for simplicity we refer to AQP9s as being the ensemble of the activity of both AQP9 and GLUT2 channels). The conductance-based formulation for ion channels proposed in the Hodgkin-Huxley model [37] is used here to describe the regulation of arsenite flux by AQP9s (Equations 1-2).…”

Section: Methodsmentioning

confidence: 99%

Mathematical model of uptake and metabolism of arsenic(III) in human hepatocytes - Incorporation of cellular antioxidant response and threshold-dependent behavior

et al. 2011

View full text Add to dashboard Cite

BackgroundArsenic is an environmental pollutant, potent human toxicant, and oxidative stress agent with a multiplicity of health effects associated with both acute and chronic exposures. A semi-mechanistic cellular-level toxicokinetic (TK) model was developed in order to describe the uptake, biotransformation and clearance of arsenical species in human hepatocytes. Notable features of this model are the incorporation of arsenic-glutathione complex formation and a "switch-like" formulation to describe the antioxidant response of hepatocytes to arsenic exposure.ResultsThe cellular-level TK model applies mass action kinetics in order to predict the concentrations of trivalent and pentavalent arsenicals in hepatocytes. The model simulates uptake of arsenite (iAsIII) via aquaporin isozymes 9 (AQP9s), glutathione (GSH) conjugation, methylation by arsenic methyltransferase (AS3MT), efflux through multidrug resistant proteins (MRPs) and the induced antioxidant response via thioredoxin reductase (TR) activity. The model was parameterized by optimization of model estimates for arsenite (iAsIII), monomethylated (MMA) and dimethylated (DMA) arsenicals concentrations with time-course experimental data in human hepatocytes for a time span of 48 hours, and dose-response data at 24 hours for a range of arsenite concentrations from 0.1 to 10 μM. Global sensitivity analysis of the model showed that at low doses the transport parameters had a dominant role, whereas at higher doses the biotransformation parameters were the most significant. A parametric comparison of the TK model with an analogous model developed for rat hepatocytes from the literature demonstrated that the biotransformation of arsenite (e.g. GSH conjugation) has a large role in explaining the variation in methylation between rats and humans.ConclusionsThe cellular-level TK model captures the temporal modes of arsenical accumulation in human hepatocytes. It highlighted the key biological processes that influence arsenic metabolism by explicitly modelling the metabolic network of GSH-adducts formation. The parametric comparison with the TK model developed for rats suggests that the variability in GSH conjugation could have an important role in inter-species variability of arsenical methylation. The TK model can be incorporated into larger-scale physiologically based toxicokinetic (PBTK) models of arsenic for improving the estimates of PBTK model parameters.

show abstract

“…Miao et al found increased AQP9 expression significantly enhanced arsenic uptake and may play a critical role in the development of arsenic resistance in human lung cancer cells. 53 Aquaporin 9 was not only important to arsenic resistance in human lung cancer cells by enhancing arsenic uptake but also plays a critical role in the development of platinum-based chemotherapy response. Aquaporin 9 might be significantly associated with chemotherapy response for patients with NSCLC but not for patients with small-cell lung cancer.…”

Section: Expression Of Aqps In Cancermentioning

confidence: 99%

Aquaporins

Wang

Zhang

et al. 2016

Technol Cancer Res Treat

View full text Add to dashboard Cite

Aquaporins are a family of integral membrane proteins that are expressed in all living organisms and play vital roles in transcellular and transepithelial water movement. Cell viability and motility are critical for progression of cancer. Cell survival requires the suitable concentration of water and solutes. The balance is largely maintained by aquaporins whose major function is the transport of water and small solutes across the plasma membrane. The important role of aquaporins has received more and more attention in the recent years. A number of recent studies have revealed that aquaporins may be involved in cell migration and angiogenesis. This review will highlight the expression of aquaporins in different malignant neoplasms. Remarkably, we will summarize the influence of drugs on aquaporins, not only the traditional Chinese medicine but also the Western medicine. Therapeutic targeting of aquaporins may thus be advantageous for blocking the mechanism common for a number of key cancer phenotypes.

show abstract

Increased aquaglyceroporin 9 expression disrupts arsenic resistance in human lung cancer cells

Cited by 20 publications

References 62 publications

Reduced arsenic clearance and increased toxicity in aquaglyceroporin-9-null mice

Reduced arsenic clearance and increased toxicity in aquaglyceroporin-9-null mice

Mathematical model of uptake and metabolism of arsenic(III) in human hepatocytes - Incorporation of cellular antioxidant response and threshold-dependent behavior

Aquaporins

Contact Info

Product

Resources

About