scholarly journals Decreased expression of cystic fibrosis transmembrane conductance regulator impairs sperm quality in aged men

Reproduction ◽  
2013 ◽  
Vol 146 (6) ◽  
pp. 637-645 ◽  
Author(s):  
Ruiying Diao ◽  
Kin Lam Fok ◽  
Li Zhao ◽  
Hao Chen ◽  
Hui Tang ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Old Age ◽  
Sperm Quality ◽  
Neck Region ◽  
Dependent Manner ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Age Dependent ◽  
Old Men ◽  
Cystic Fibrosis Transmembrane

Sperm quality declines with aging; however, the underlying molecular mechanism remains elusive. The cystic fibrosis transmembrane conductance regulator (CFTR) has been shown to play an essential role in fertilizing capacity of sperm and male fertility. This study aimed to investigate the involvement of age-dependent CFTR downregulation in lowering sperm quality in old age. Two hundred and one healthy fertile men of three age groups (20–40 years,n=64; 40–60 years,n=61; and >60 years,n=76) were recruited. Expression of CFTR was determined by RT-PCR, western blot, and immunofluorescence staining. Collected sperm were treated with CFTR inhibitor or potentiator. Sperm quality was assessed by motility and bicarbonate-induced capacitation. The results showed that the expression of CFTR on the equatorial segment and neck region of sperm was significantly decreased in an age-dependent manner. Reduction of CFTR expression in sperm from old men was correlated with lowered forward motility and decreased HCO3−sensitivity required for sperm capacitation. Activation of CFTR by genistein partially rescued the decreased forward motility in sperm from old men. Decreased CFTR expression in sperm was also found to be associated with lowered sperm quality in aging mice. These results suggest that age-dependent downregulation of CFTR in sperm leads to lowered sperm quality in old age sperm. CFTR may be a pontential target for rescuing sperm motility as well as a fertility indicator in old age men.

Rectification of whole cell cystic fibrosis transmembrane conductance regulator chloride current

1995 ◽  
Vol 268 (3) ◽  
pp. C636-C646 ◽  
Author(s):  
J. L. Overholt ◽  
A. Saulino ◽  
M. L. Drumm ◽  
R. D. Harvey
Keyword(s):  
Cystic Fibrosis ◽  
Theory Model ◽  
Rate Theory ◽  
Dependent Manner ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Concentration Dependent Manner ◽  
Whole Cell ◽  
Multiple Binding Sites ◽  
Cystic Fibrosis Transmembrane

Whole cell epithelial cystic fibrosis transmembrane conductance regulator (CFTR) Cl- currents exhibited a linear current-voltage (I-V) relationship with high symmetrical transmembrane Cl- concentrations. However, when intracellular Cl- (Cli-) was reduced by replacement with glutamate, I-V relationships were outwardly rectifying. Rectification was not affected by reducing extracellular Cl- to eliminate or reverse the gradient, indicating that rectification is not a function of the Cl- gradient. Rectification was affected by Cli- in a concentration-dependent manner, and it was weaker when Cli- was reduced by replacement with sucrose. These characteristics are identical to those of the cardiac isoform of CFTR, and the experimental data could be simulated by an Eyring rate theory model assuming that permeating anions interact at a single binding site within the channel pore. No evidence was found for multiple binding sites. These results indicate that rectification is a function of the concentration and permeability of the anions inside the cell. It is concluded that rectification of CFTR Cl- current is a property of ion channel permeation that would occur under physiological conditions and that permeation of the epithelial and cardiac isoforms of CFTR is identical.

Fluoride stimulates cystic fibrosis transmembrane conductance regulator Cl− channel activity

1998 ◽  
Vol 274 (3) ◽  
pp. L305-L312 ◽  
Author(s):  
Herbert A. Berger ◽  
Sue M. Travis ◽  
Michael J. Welsh
Keyword(s):  
Cystic Fibrosis ◽  
Single Channel ◽  
Single Channels ◽  
Dependent Manner ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Binding Domains ◽  
Cytosolic Domains ◽  
Cystic Fibrosis Transmembrane ◽  
Dose Dependent

While studying the regulation of the cystic fibrosis transmembrane conductance regulator (CFTR), we found that addition of F− to the cytosolic surface of excised, inside-out membrane patches reversibly increased Cl− current in a dose-dependent manner. Stimulation required prior phosphorylation and the presence of ATP. F− increased current even in the presence of deferoxamine, which chelates Al3+, suggesting that stimulation was not due to A[Formula: see text]. F− also stimulated current in a CFTR variant that lacked a large part of the R domain, suggesting that the effect was not mediated via this domain. Studies of single channels showed that F−increased the open-state probability by slowing channel closure from bursts of activity; the mean closed time between bursts and single-channel conductance was not altered. These results suggested that F− influenced regulation by the cytosolic domains, most likely the nucleotide-binding domains (NBDs). Consistent with this, we found that mutation of a conserved Walker lysine in NBD2 changed the relative stimulatory effect of F− compared with wild-type CFTR, whereas mutation of the Walker lysine in NBD1 had no effect. Based on these and previous data, we speculate that F− interacts with CFTR, possibly via NBD2, and slows the rate of channel closure.

Sign in / Sign up

Export Citation Format

Share Document