1,721,137 research outputs found
The Electrogenic Chloride Exchanger ClC5 as a Novel Player in Renal Cysts in Tuberous Sclerosis
Full text linkRenal cystic diseases are complex and multifaceted disorders that can have genetic or nongenetic bases. The etiology of these disorders is not unique but may be associated with other systemic diseases, acquired or inherited. With significant progress in genetics, several mutated genes have been associated with renal cyst development. Different abnormal protein functions, causing different renal cystic diseases, imply that several molecular mechanisms may lead to the formation of cysts. Cysts can be generated from any tract of the nephron; they usually generate in the distal nephron and in the collecting ducts.1 Autosomal dominant polycystic kidney disease (ADPKD) is the most common cystic disorder, caused by mutations in the genes coding for polycystin-1 and polycystin-2. Renal cysts are also found in 50% of patients with tuberous sclerosis complex (TSC).2 Patients with TSC can develop several disturbances, affecting many organs. Neurologic symptoms are often described, although renal defects can be considered the second most common features in TSC-affected individuals. In this issue of The American Journal of Pathology, Barone et al3 proposed the electrogenic exchanger ClC5 as a possible candidate for mediating chloride secretion into the renal cyst lumen in TSC
History of Diabetes Insipidus
Full text linkUnder physiological conditions, fluid and electrolyte homoeostasis is maintained by the kidney adjusting urine volume and composition according to body needs. Diabetes Insipidus is a complex and heterogeneous clinical syndrome affecting water balance and characterized by constant diuresis, resulting in large volumes of dilute urine. With respect to the similarly named Diabetes Mellitus, a disease already known in ancient Egypt, Greece and Asia, Diabetes Insipidus has been described several thousand years later. In 1670s Thomas Willis, noted the difference in taste of urine from polyuric subjects compared with healthy individuals and started the differentiation of Diabetes Mellitus from the more rare entity of Diabetes Insipidus. In 1794, Johann Peter Frank described polyuric patients excreting nonsaccharine urine and introduced the term of Diabetes Insipidus. An hystorical milestone was the in 1913, when Farini successfully used posterior pituitary extracts to treat Diabetes Insipidus. Until 1920s the available evidence indicated Diabetes Insipidus as a disorder of the pituitary gland. In the early 1928, De Lange first observed that some patients with Diabetes Insipidus did not respond to posterior pituitary extracts and subsequently Forssman and Waring in 1945 established that the kidney had a critical role for these forms of Diabetes Insipidus resistant to this treatment. In 1947 Williams and Henry introduced the term Nephrogenic Diabetes Insipidus for the congenital syndrome characterized by polyuria and renal concentrating defect resistant to vasopressin. In 1955, du Vigneaud received the 1955 Nobel Prize in chemistry for the first synthesis of the hormone vasopressin representing a milestone for the treatment of Central Diabetes Insipidus
Evaluating the oxidative stress in renal diseases: What is the role for s-glutathionylation?
No full textSignificance: Reactive oxygen species (ROS) have long been considered as toxic derivatives of aerobic metabolism displaying a harmful effect to living cells. Deregulation of redox homeostasis and production of excessive free radicals may contribute to the pathogenesis of kidney diseases. In line, oxidative stress increases in patients with renal dysfunctions due to a general increase of ROS paralleled by impaired antioxidant ability. Recent Advances: Emerging evidence revealed that physiologically, ROS can act as signaling molecules interplaying with several transduction pathways such as proliferation, differentiation, and apoptosis. ROS can exert signaling functions by modulating, at different layers, protein oxidation since proteins have "cysteine switches" that can be reversibly reduced or oxidized, supporting the dynamic signaling regulation function. In this scenario, S-glutathionylation is a posttranslational modification involved in oxidative cellular response. Critical Issues: Although it is widely accepted that renal dysfunctions are often associated with altered redox signaling, the relative role of S-glutathionylation on the pathogenesis of specific renal diseases remains unclear and needs further investigations. In this review, we discuss the impact of ROS in renal health and diseases and the role of selective S-glutathionylation proteins potentially relevant to renal physiology. Future Directions: The paucity of studies linking the reversible protein glutathionylation with specific renal disorders remains unmet. The growing number of S-glutathionylated proteins indicates that this is a fascinating area of research. In this respect, further studies on the association of reversible glutathionylation with renal diseases, characterized by oxidative stress, may be useful to develop new pharmacological molecules targeting protein S-glutathionylation
Functional interplay between CFTR and pendrin: physiological and pathophysiological relevance
Full text link: The transport of chloride and bicarbonate across epithelia controls the pH and volume of the intracellular and luminal fluids, as well as the systemic pH and vascular volume. The anion exchanger pendrin (SLC26A4) and the cystic fibrosis transmembrane conductance regulator (CFTR) channel are expressed in the apical membrane of epithelial cells of various organs and tissues, including the airways, kidney, thyroid, and inner ear. While pendrin drives chloride reabsorption and bicarbonate, thiocyanate or iodide secretion within the apical compartment, CFTR represents a pathway for the apical efflux of chloride, bicarbonate, and possibly iodide. In the airways, pendrin and CFTR seems to be involved in alkalinization of the apical fluid via bicarbonate secretion, especially during inflammation, while CFTR also controls the volume of the apical fluid via a cAMP-dependent chloride secretion, which is stimulated by pendrin. In the kidney, pendrin is expressed in the cortical collecting duct and connecting tubule and co-localizes with CFTR in the apical membrane of β intercalated cells. Bicarbonate secretion occurs via pendrin, which also drives chloride reabsorption. A functional CFTR is required for pendrin activity. Whether CFTR stimulates pendrin via a direct molecular interaction or other mechanisms, or simply provides a pathway for chloride recycling across the apical membrane remains to be established. In the thyroid, CFTR and pendrin might have overlapping functions in driving the apical flux of iodide within the follicular lumen. In other organs, including the inner ear, the possible functional interplay between pendrin and CFTR needs to be explored
Recruitment of F-actin and the actin-binding protein moesin in the membrane protrusion during cell swelling
No full textCell swelling causes actin remodeling and recruitment of the ERM moesin in membrane protrusions in collecting duct principal cells
No full textAquaporins in Health and Disease: New Molecular Targets for Drug Discovery
No full textThe localization of the water channel aquaporin-2 (AQP2) is subjected to regulation
by vasopressin. Vasopressin adjusts the amount of AQP2 in the plasma membrane
by regulating its redistribution from intracellular vesicles into the plasma membrane allowing
water entry into the cells and water exit through AQP3 and AQP4. This permits water
reabsorption and urine concentration. Following binding of vasopressin to its V2R receptor,
the rise in cAMP activates protein kinase A, which in turn phosphorylates AQP2 and
thereby triggers the redistribution of AQP2. Several proteins participating in the control of cAMP-dependent AQP2 trafficking have been identified including SNAREs, annexin-2,
hsc70, AKAPs and small GTPases of the Rho family proteins. Moreover, AQP2 has been
found to be regulated by posttranslational modifications (PTMs), such as ubiquitination
and glutathionylation. Loss-of-function mutations of both V2R and AQP2 are associated
with congenital nephrogenic diabetes insipidus characterized by a failure to concentrate
urine. Conversely gain-of-function mutations of the V2R are associated with the nephrogenic
syndrome of inappropriate antidiuresis characterized by positive water balance
and hyponatremia. Vaptans, nonpeptide vasopressin receptor antagonists represent a new
class of drugs developed for the treatment of euvolemic or hypervolemic hyponatremia.
This chapter summarizes recent data elucidating molecular mechanisms underlying the
trafficking of AQP2. The mechanism of action of vaptans and their current use in clinical
practice is discussed
Cell swelling causes actin reorganization and recruitment of the actin binding protein moesin in membrane protrusions in collecting duct principal cells
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