The effect of sphingomyelin synthase 2 (SMS2) deficiency on the expression of drug transporters in mouse brain

Dong, Jianyu; Zhu, Xingang; Wang, Weirong; Yang, Qing

doi:10.1016/j.bcp.2011.04.009

Cited by 28 publications

(26 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We previously showed that P‐gp localization and function are also regulated by ERM proteins in the intestine . On the other hand, in the liver, Rdx alone controls P‐gp, while in brain capillary endothelial cells, ezrin (Ezr) and moesin (Msn) are involved in the membrane expression and transport function of P‐gp . We and other researchers have shown that P‐gp membrane localization and function are regulated by Rdx in the intestine .…”

Section: Introductionmentioning

confidence: 54%

Regulation of breast cancer resistance protein and P-glycoprotein by ezrin, radixin and moesin in lung, intestinal and renal cancer cell lines

Yano

Okabe

Fujii

et al. 2020

Journal of Pharmacy and Pharmacology

View full text Add to dashboard Cite

Objectives Ezrin (Ezr), radixin (Rdx) and moesin (Msn) (ERM) proteins anchor other proteins to the cell membrane, serving to regulate their localization and function. Here, we examined whether ERM proteins functionally regulate breast cancer resistance protein (BCRP) and P‐glycoprotein in cell lines derived from lung, intestinal and renal cancers. Methods ERM proteins were each silenced with appropriate siRNA. BCRP and P‐gp functions were evaluated by means of efflux and uptake assays using 7‐ethyl‐10‐hydroxycamptothecin (SN‐38) and rhodamine123 (Rho123) as specific substrates, respectively, in non‐small cell lung cancer HCC827 cells, intestinal cancer Caco‐2 cells and renal cancer Caki‐1 cells. Key findings In HCC827 cells, the efflux rates of SN‐38 and Rho123 were significantly decreased by knockdown of Ezr or Msn, but not Rdx. However, BCRP function was unaffected by Ezr or Rdx knockdown in Caco‐2 cells, which do not express Msn. In Caki‐1 cells, Rdx knockdown increased the intracellular SN‐38 concentration, while knockdown of Ezr or Msn had no effect. Conclusions Our findings indicate that regulation of BCRP and P‐gp functions by ERM proteins is organ‐specific. Thus, if the appropriate ERM protein(s) are functionally suppressed, accumulation of BCRP or P‐gp substrates in lung, intestine or kidney cancer tissue might be specifically increased.

show abstract

Section: Introductionmentioning

confidence: 54%

Regulation of breast cancer resistance protein and P-glycoprotein by ezrin, radixin and moesin in lung, intestinal and renal cancer cell lines

Yano

Okabe

Fujii

et al. 2020

Journal of Pharmacy and Pharmacology

View full text Add to dashboard Cite

show abstract

“…Indirect evidence for SM-induced ABCB1 transcriptional upregulation has been reported in the brain of SMS2-deficient mice [248]. In the absence of SMS2, ABCB1 mRNA, protein and transport activity were diminished but how changes of SM levels signal from PM, where SMS2 is normally localized, to the transcriptional machinery is unknown.…”

Section: Rendering the Mdr Phenotype And Altered Sphingolipids: Chmentioning

confidence: 99%

Sphingolipid abnormalities in cancer multidrug resistance: Chicken or egg?

Lee

Kolesnick

2017

Cellular Signalling

View full text Add to dashboard Cite

The cancer multidrug resistance (MDR) phenotype encompasses a myriad of molecular, genetic and cellular alterations resulting from progressive oncogenic transformation and selection. Drug efflux transporters, in particular the MDR P-glycoprotein ABCB1, play an important role in MDR but cannot confer the complete phenotype alone indicating parallel alterations are prerequisite. Sphingolipids are essential constituents of lipid raft domains and directly participate in functionalization of transmembrane proteins, including providing an optimal lipid microenvironment for multidrug transporters, and are also perturbed in cancer. Here we postulate that increased sphingomyelin content, developing early in some cancers, recruits and functionalizes plasma membrane ABCB1 conferring a state of partial MDR, which is completed by glycosphingolipid disturbance and the appearance of intracellular vesicular ABCB1. In this review, the independent and interdependent roles of sphingolipid alterations and ABCB1 upregulation during the transformation process and resultant conferment of partial and complete MDR phenotypes are discussed.

show abstract

“…SMS2 defi ciency, on the other hand, ameliorates high fat-induced obesity ( 16,17 ), attenuates lipopolysaccharide-induced lung injury ( 18 ), and reduces atherosclerosis ( 19 ). A recent study investigating SMS2 defi ciency in the brain reported decreased expression and altered function of drug transporters ( 20 ).…”

Section: Generation Of the Conditional Smsrdelex6 Vectormentioning

confidence: 99%

Functional characterization of enzymes catalyzing ceramide phosphoethanolamine biosynthesis in mice

Bickert

Ginkel

Kol

et al. 2015

Journal of Lipid Research

View full text Add to dashboard Cite

The effect of sphingomyelin synthase 2 (SMS2) deficiency on the expression of drug transporters in mouse brain

Cited by 28 publications

References 29 publications

Regulation of breast cancer resistance protein and P-glycoprotein by ezrin, radixin and moesin in lung, intestinal and renal cancer cell lines

Regulation of breast cancer resistance protein and P-glycoprotein by ezrin, radixin and moesin in lung, intestinal and renal cancer cell lines

Sphingolipid abnormalities in cancer multidrug resistance: Chicken or egg?

Functional characterization of enzymes catalyzing ceramide phosphoethanolamine biosynthesis in mice

Contact Info

Product

Resources

About