scholarly journals Nonpigmented Ciliary Epithelial Cells Respond to Acetazolamide by a Soluble Adenylyl Cyclase Mechanism

2014 ◽  
Vol 55 (1) ◽  
pp. 187 ◽  
Author(s):  
Mohammad Shahidullah ◽  
Amritlal Mandal ◽  
Guojun Wei ◽  
Lonny R. Levin ◽  
Jochen Buck ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Adenylyl Cyclase ◽  
Soluble Adenylyl Cyclase ◽  
Nonpigmented Ciliary Epithelial

Regulation of CFTR channels by HCO3−-sensitive soluble adenylyl cyclase in human airway epithelial cells

2005 ◽  
Vol 289 (5) ◽  
pp. C1145-C1151 ◽  
Author(s):  
Yan Wang ◽  
Chak Sum Lam ◽  
Fan Wu ◽  
Wen Wang ◽  
Yuanyuan Duan ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Adenylyl Cyclase ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Adenylyl Cyclases ◽  
Open Probability ◽  
Soluble Adenylyl Cyclase ◽  
Human Airway ◽  
Human Airway Epithelium ◽  
Polymerase Chain

CFTR channels conduct HCO3− in addition to Cl− in airway epithelial cells. A defective HCO3−-transporting function of CFTR may underlie the pathogenesis of cystic fibrosis. In the present study, we have investigated whether a HCO3−-sensitive soluble adenylyl cyclase (sAC) is functionally coupled with CFTR and thus forms an autoregulatory mechanism for HCO3− transport in human airway epithelial Calu-3 cells. A reverse transcriptase-polymerase chain reaction showed that transcripts of both full-length and truncated sACs are present in Calu-3 cells. Truncated sAC protein is the predominant, if not the only, isoform expressed in Calu-3 cells. HCO3− stimulated a modest increase in cAMP production, and the increase was sensitive to 2-hydroxyestradiol (2-HE), a sAC inhibitor, but not to SQ22,536, a blocker of conventional transmembrane adenylyl cyclases. These results suggest that sAC is functional in Calu-3 cells. Adding 25 mM HCO3− to the bath stimulated CFTR-mediated whole cell currents in the absence, but not in the presence, of 2-HE. In cell-attached membrane patches, 25 or 50 mM HCO3− in the bath markedly increased the product of channel number and open probability of CFTR, and this activation was attenuated by 2-HE. These findings demonstrate that sAC signaling pathway is involved in the regulation of CFTR function in human airway epithelium and thereby provides a link between the level of intracellular HCO3−/CO2 and the modulation of HCO3−-conductive CFTR function by cAMP/PKA.

Two domains are critical for the nuclear localization of soluble adenylyl cyclase

Biochimie ◽  
2006 ◽  
Vol 88 (3-4) ◽  
pp. 319-328 ◽  
Author(s):  
Q FENG ◽  
Y ZHANG ◽  
Y LI ◽  
Z LIU ◽  
J ZUO ◽  
...  
Keyword(s):  
Adenylyl Cyclase ◽  
Nuclear Localization ◽  
Soluble Adenylyl Cyclase

scholarly journals Non-canonical regulation of glycogenolysis and the Warburg phenotype by soluble adenylyl cyclase

2020 ◽  
Author(s):  
Jung-Chin Chang ◽  
Simei Go ◽  
Eduardo H. Gilglioni ◽  
Hang Lam Li ◽  
Hsu-Li Huang ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Adenylyl Cyclase ◽  
Energy Homeostasis ◽  
Aerobic Glycolysis ◽  
Glycogen Metabolism ◽  
Adenylyl Cyclases ◽  
Soluble Adenylyl Cyclase ◽  
Atp Level ◽  
Downstream Effectors ◽  
Different Types

AbstractCyclic AMP is produced in cells by two very different types of adenylyl cyclases: the canonical transmembrane adenylyl cyclases (tmACs, ADCY1∼9) and the evolutionarily more conserved soluble adenylyl cyclase (sAC, ADCY10). While the role and regulation of tmACs is well documented, much less is known of sAC in cellular metabolism. We demonstrate here that sAC is an acute regulator of glycolysis, oxidative phosphorylation and glycogen metabolism, tuning their relative bioenergetic contributions. Suppression of sAC activity leads to aerobic glycolysis, enhanced glycogenolysis, decreased oxidative phosphorylation, and an elevated cytosolic NADH/NAD+ ratio, resembling the Warburg phenotype. Importantly, we found that glycogen metabolism is regulated in opposite directions by cAMP depending on its location of synthesis and downstream effectors. While the canonical tmAC-cAMP-PKA axis promotes glycogenolysis, we identify a novel sAC-cAMP-Epac1 axis that suppresses glycogenolysis. These data suggest that sAC is an autonomous bioenergetic sensor that suppresses aerobic glycolysis and glycogenolysis when ATP levels suffice. When the ATP level falls, diminished sAC activity induces glycogenolysis and aerobic glycolysis to maintain energy homeostasis.

Sign in / Sign up

Export Citation Format

Share Document