ABCC7 p.Thr1478*
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[hide] Purinergic signaling underlies CFTR control of hum... J Cyst Fibros. 2004 Jun;3(2):99-117. Braunstein GM, Zsembery A, Tucker TA, Schwiebert EM
Purinergic signaling underlies CFTR control of human airway epithelial cell volume.
J Cyst Fibros. 2004 Jun;3(2):99-117., [PMID:15463893]
Abstract [show]
BACKGROUND: Loss of cystic fibrosis transmembrane conductance regulator (CFTR) function in cystic fibrosis (CF) causes dysregulation of multiple ion channels, water channels, and acid-base transporters in epithelia. As such, we hypothesized that dysregulation of many critical ion channels and transporters may cause defects in human airway epithelial cell volume regulation. METHODS: Cell volume, regulatory volume decrease, and its regulation was assessed in real-time via Coulter Counter Multisizer III-driven electronic cell sizing in non-CF, CF, and CFTR-complemented CF human airway epithelial cells. SPQ halide fluorescence assay of hypotonicity-induced chloride efflux provided indirect validation of the cell volume assays. RESULTS: CFTR, via autocrine ATP signaling, governs human airway epithelial cell volume regulation. Non-CF cells and wild-type (WT)-CFTR-transfected CF cells had normal regulatory volume decrease (RVD) responses that were attenuated by blockade of autocrine and paracrine purinergic signaling. In contrast, parental IB3-1 CF cells or IB3-1 cells expressing CFTR mutants (DeltaF508, G551D, and S1455X) failed to RVD. CF cell RVD was rescued by agonists to P2Y G protein-coupled receptors and, more robustly, by agonists to P2X purinergic receptor channels. CONCLUSIONS: Loss of CFTR and CFTR-driven autocrine ATP signaling may underlie defective cell volume regulation and dysregulated ion, water, and acid-base transport in CF airway epithelia.
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No. Sentence Comment
119 IB3-1 cells express the DF508-CFTR and W1282X-CFTR mutations endogenously [35,49].
X
ABCC7 p.Thr1478* 15463893:119:40
status: NEW121 No CFTR protein was detectable in ''mock controls``, while band B ''core glycosylated`` (130-140 kDa) and band C ''maturely glycosylated`` (160-180 kDa) forms of CFTR were found for WT-CFTR, T1478X (also DTRL)-CFTR, S1455X-CFTR, and G551D-CFTR [9,51,52].
X
ABCC7 p.Thr1478* 15463893:121:191
status: NEW122 S1455X-CFTR showed a similar profile to T1478X-CFTR (data not shown).
X
ABCC7 p.Thr1478* 15463893:122:40
status: NEW172 When compared to empty vector, WT-CFTR and T1478X-CFTR were able to fully recover their cell volume after hypotonic cell swelling Fig. 3.
X
ABCC7 p.Thr1478* 15463893:172:43
status: NEW204 The IB3-1 cells transiently transfected with WT- and T1478X-CFTR showed an increase in chloride permeability and increased rate of ClÀ release in response to 25% hypotonic shock (Fig. 5B).
X
ABCC7 p.Thr1478* 15463893:204:53
status: NEW216 IB3-1 cells expressing WT- and T1478X-CFTR showed a marked increase in magnitude of chloride efflux as well as increased rate of chloride release (n = 3-4 experiments for each construct, asterisk indicates P < 0.01 versus empty vector control, cross indicates P < 0.05 versus empty vector control).
X
ABCC7 p.Thr1478* 15463893:216:31
status: NEW118 No CFTR protein was detectable in ''mock controls``, while band B ''core glycosylated`` (130-140 kDa) and band C ''maturely glycosylated`` (160-180 kDa) forms of CFTR were found for WT-CFTR, T1478X (also DTRL)-CFTR, S1455X-CFTR, and G551D-CFTR [9,51,52].
X
ABCC7 p.Thr1478* 15463893:118:191
status: NEW167 When compared to empty vector, WT-CFTR and T1478X-CFTR were able to fully recover their cell volume after hypotonic cell swelling Fig. 3.
X
ABCC7 p.Thr1478* 15463893:167:43
status: NEW199 The IB3-1 cells transiently transfected with WTand T1478X-CFTR showed an increase in chloride permeability and increased rate of Cl release in response to 25% hypotonic shock (Fig. 5B).
X
ABCC7 p.Thr1478* 15463893:199:51
status: NEW211 IB3-1 cells expressing WTand T1478X-CFTR showed a marked increase in magnitude of chloride efflux as well as increased rate of chloride release (n = 3-4 experiments for each construct, asterisk indicates P < 0.01 versus empty vector control, cross indicates P < 0.05 versus empty vector control).
X
ABCC7 p.Thr1478* 15463893:211:29
status: NEW