4 research outputs found
Regulation of the V-ATPase in kidney epithelial cells: dual role in acid–base homeostasis and vesicle trafficking
The proton-pumping V-ATPase is a complex, multi-subunit enzyme that is
highly expressed in the plasma membranes of some epithelial cells in the
kidney, including collecting duct intercalated cells. It is also located on
the limiting membranes of intracellular organelles in the degradative and
secretory pathways of all cells. Different isoforms of some V-ATPase subunits
are involved in the targeting of the proton pump to its various intracellular
locations, where it functions in transporting protons out of the cell across
the plasma membrane or acidifying intracellular compartments. The former
process plays a critical role in proton secretion by the kidney and regulates
systemic acid–base status whereas the latter process is central to
intracellular vesicle trafficking, membrane recycling and the degradative
pathway in cells. We will focus our discussion on two cell types in the
kidney: (1) intercalated cells, in which proton secretion is controlled by
shuttling V-ATPase complexes back and forth between the plasma membrane and
highly-specialized intracellular vesicles, and (2) proximal tubule cells, in
which the endocytotic pathway that retrieves proteins from the glomerular
ultrafiltrate requires V-ATPase-dependent acidification of post-endocytotic
vesicles. The regulation of both of these activities depends upon the ability
of cells to monitor the pH and/or bicarbonate content of their extracellular
environment and intracellular compartments. Recent information about these
pH-sensing mechanisms, which include the role of the V-ATPase itself as a pH
sensor and the soluble adenylyl cyclase as a bicarbonate sensor, will be
addressed in this review
Sex-dependent differences in water homeostasis in wild-type and V-ATPase B1-subunit deficient mice.
Men tend to dehydrate more than women after prolonged exercise, possibly due to lower water intake and higher perspiration rate. Women are prone to exercise-associated hyponatremia, primarily attributed to the higher water consumption causing hypervolemia. Since aquaporin-2 (AQP2) water channels in the kidney collecting duct (CD) principal cells (PCs) are involved in maintaining water balance, we investigated their role in sex-dependent water homeostasis in wild-type (WT) C57BL/6 mice. Because CD intercalated cells (ICs) may also be involved in water balance, we also assessed the urine concentrating ability of V-ATPase B1 subunit-deficient (Atp6v1b1-/-) mice. Upon 12-hour water deprivation, urine osmolality increased by 59% in WT female mice and by only 28% in males. This difference was abolished in Atp6v1b1-/- mice, in which dehydration induced a ~30% increase in urine osmolarity in both sexes. AQP2 levels were highest in WT females; female Atp6v1b1-/- mice had substantially lower AQP2 expression than WT females, comparable to the low AQP2 levels seen in both Atp6v1b1-/- and WT males. After dehydration, AQP2 relocates towards the PC apical pole, especially in the inner stripe and inner medulla, and to a greater extent in WT females than in WT males. This apparent sex-dependent concentrating advantage was absent in Atp6v1b1-/- females, whose reduced AQP2 apical relocation was similar to WT males. Accordingly, female mice concentrate urine better than males upon dehydration due to increased AQP2 expression and mobilization. Moreover, our data support the involvement of ICs in water homeostasis, at least partly mediated by V-ATPase, in a sex-dependent manner
International consensus statement on allergy and rhinology: Olfaction.
BACKGROUND
The literature regarding clinical olfaction, olfactory loss, and olfactory dysfunction has expanded rapidly over the past two decades, with an exponential rise in the past year. There is substantial variability in the quality of this literature and a need to consolidate and critically review the evidence. It is with that aim that we have gathered experts from around the world to produce this International Consensus on Allergy and Rhinology: Olfaction (ICAR:O).
METHODS
Using previously described methodology, specific topics were developed relating to olfaction. Each topic was assigned a literature review, evidence-based review, or evidence-based review with recommendations format as dictated by available evidence and scope within the ICAR:O document. Following iterative reviews of each topic, the ICAR:O document was integrated and reviewed by all authors for final consensus.
RESULTS
The ICAR:O document reviews nearly 100 separate topics within the realm of olfaction, including diagnosis, epidemiology, disease burden, diagnosis, testing, etiology, treatment, and associated pathologies.
CONCLUSION
This critical review of the existing clinical olfaction literature provides much needed insight and clarity into the evaluation, diagnosis, and treatment of patients with olfactory dysfunction, while also clearly delineating gaps in our knowledge and evidence base that we should investigate further
International consensus statement on allergy and rhinology: Olfaction
Background: The literature regarding clinical olfaction, olfactory loss, and olfactory dysfunction has expanded rapidly over the past two decades, with an exponential rise in the past year. There is substantial variability in the quality of this literature and a need to consolidate and critically review the evidence. It is with that aim that we have gathered experts from around the world to produce this International Consensus on Allergy and Rhinology: Olfaction (ICAR:O). Methods: Using previously described methodology, specific topics were developed relating to olfaction. Each topic was assigned a literature review, evidence-based review, or evidence-based review with recommendations format as dictated by available evidence and scope within the ICAR:O document. Following iterative reviews of each topic, the ICAR:O document was integrated and reviewed by all authors for final consensus. Results: The ICAR:O document reviews nearly 100 separate topics within the realm of olfaction, including diagnosis, epidemiology, disease burden, diagnosis, testing, etiology, treatment, and associated pathologies. Conclusion: This critical review of the existing clinical olfaction literature provides much needed insight and clarity into the evaluation, diagnosis, and treatment of patients with olfactory dysfunction, while also clearly delineating gaps in our knowledge and evidence base that we should investigate further