PMID- 21157003
OWN - NLM
STAT- MEDLINE
DCOM- 20110407
LR  - 20191111
IS  - 0231-5882 (Print)
IS  - 0231-5882 (Linking)
VI  - 29
IP  - 4
DP  - 2010 Dec
TI  - Effect of thapsigargin on P-glycoprotein-negative and P-glycoprotein-positive 
      L1210 mouse leukaemia cells.
PG  - 396-401
AB  - Expression of drug-transporting P-glycoprotein (P-gp, an integral protein of the 
      plasma membrane) in neoplastic cells confers multidrug resistance and also 
      involves alteration of cell sensitivity to inhibitors of the sarco/endoplasmic 
      reticulum calcium pump thapsigargin (Th). Mouse leukaemia L1210 cell sublines 
      that overexpress P-gp due to selection with vincristine (R) or stable 
      transfection with a gene encoding human P-gp (T) were less sensitive to Th than 
      the parental cell line (S). Th at a concentration of 0.1 mumol/l did not induce 
      alterations in the amount of P-gp mRNA in R or T cells (S cells did not contain 
      any measurable amount of this transcript as assessed by RT-PCR) or in the amount 
      of calnexin (CNX) or glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in all 
      three cell sublines. However, when using a concentration of 10 mumol/l, Th 
      decreases the amounts of CNX, GAPDH (in S, R and T cells) and P-gp (in R and T 
      cells) mRNAs. In contrast to R and T cells (which contain abundant P-gp), S cells 
      did not contain any P-gp detectable by the c219 antibody on a Western blot. Th at 
      a concentration of 0.1 mumol/l induced a reduction in the amount of P-gp present 
      in R and T cells, particularly in isoforms with higher molecular weights (i.e., 
      mature fully glycosylated isoforms). Similar results were observed when Th was 
      used at a concentration of 10 mumol/l. R and T cells contained lower levels of CNX 
      than S cells. While Th at a lower concentration did not alter the levels of CNX 
      in S, R or T cells, a higher concentration of this substance induced a measurable 
      decrease in the amount of CNX. S, R and T cells did not differ with respect to 
      GAPDH content, but Th induced a reduction in the amount of this protein in all 
      cell sublines. More pronounced results were observed when Th was applied at a 
      concentration of 10 mumol/l comparing with a concentration of 0.1 mmol/l. These 
      changes may be involved together with the Th efflux activity of P-gp in 
      Th-resistance associated with the P-gp-mediated multidrug resistance of R and T 
      cells.
FAU - Seres, Mario
AU  - Seres M
AD  - Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, 
      Vlarska 5, 833 34 Bratislava, Slovakia.
FAU - Ditte, Peter
AU  - Ditte P
FAU - Breier, Albert
AU  - Breier A
FAU - Sulova, Zdena
AU  - Sulova Z
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Slovakia
TA  - Gen Physiol Biophys
JT  - General physiology and biophysics
JID - 8400604
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B)
RN  - 0 (RNA, Messenger)
RN  - 139873-08-8 (Calnexin)
RN  - 5J49Q6B70F (Vincristine)
RN  - 67526-95-8 (Thapsigargin)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B/genetics/*metabolism
MH  - Animals
MH  - Calnexin/genetics/metabolism
MH  - Cell Death/drug effects
MH  - Cell Line, Tumor
MH  - Dose-Response Relationship, Drug
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Leukemia L1210/genetics/metabolism/*pathology
MH  - Mice
MH  - RNA, Messenger/genetics/metabolism
MH  - Thapsigargin/*pharmacology
MH  - Transfection
MH  - Vincristine/pharmacology
EDAT- 2010/12/16 06:00
MHDA- 2011/04/08 06:00
CRDT- 2010/12/16 06:00
PHST- 2010/12/16 06:00 [entrez]
PHST- 2010/12/16 06:00 [pubmed]
PHST- 2011/04/08 06:00 [medline]
AID - 10.4149/gpb_2010_04_396 [doi]
PST - ppublish
SO  - Gen Physiol Biophys. 2010 Dec;29(4):396-401. doi: 10.4149/gpb_2010_04_396.