Stingrays' blood pH regulated by identified proton pump function
In a groundbreaking discovery, researchers at the University of California San Diego, led by Martíñ Tresguerres, a marine biologist at Scripps, have uncovered the role of a crucial enzyme in the regulation of blood pH in stingrays and its potential implications for human kidney function. The study, published in the August issue of the American Journal of Physiology - Cell Physiology, focuses on the vacuolar-type H+-ATPase (VHA) proton pump.
The study aimed to shed light on the enzyme's function in human kidneys, regulating blood and urine functions, as well as its varying roles in a range of organisms, including bone-eating worms and corals. The Scripps researchers believe that the proton pump may have a similar function in stingrays and in human kidneys to regulate blood pH.
The cellular activity results in the transport of acid to the blood and the return of blood pH to normal levels. In stingrays and other fish, VHA is involved in regulating blood pH by excreting protons into the surrounding water or moving them across internal membranes, helping maintain acid-base homeostasis under varying environmental conditions.
The enzyme, called a proton pump and abbreviated VHA, activates when pH is elevated and more alkaline, moving from the cell's inner cytoplasm to the outer membrane to push excess acid out of the cell. Scripps graduate student Jinae Roa isolated cells from stingray gills and exposed them to varying pH conditions to analyze the enzyme's cellular-level function.
The findings of the study could inform biomedical research on kidney functions in humans, including disorders of acid-base balance. Understanding the function of VHA in stingrays can illuminate fundamental mechanisms of proton transport and pH regulation that are evolutionarily conserved. This knowledge could potentially guide the development of treatments targeting proton pumps or related pathways to manage conditions like metabolic acidosis or renal tubular acidosis.
The research was funded by the National Science Foundation, a Alfred P. Sloan Research Fellowship, and the American Physiological Society's William Townsend Porter Pre-doctoral Fellowship. The study's lead author, Jinae Roa, is focusing her PhD research on understanding how pH is sensed and regulated in rays, sharks, hagfish, and other fishes.
Rays are considered a great model organism for studying pH regulation due to their large cells that can be studied in isolation apart from their whole body. The proton pump is present in every animal, suggesting that this study may help better target the underlying mechanism for pH-related illnesses such as diabetic ketoacidosis and kidney stones in mammals, including humans.
In corals, the enzyme promotes photosynthesis in cooperation with symbiotic algae that live inside the cells to help provide the food needed to survive in warm, nutrient-poor environments. Osedax, a genus of mouthless and gutless "boneworms," uses the acid-secreting enzyme to dissolve whale bones to access the nutrients inside.
Keeping individual cells alive outside of the human body to study exactly how the proton pump works is extremely difficult. However, the study's findings provide a significant step forward in understanding the enzyme's role in maintaining acid-base balance, both in aquatic animals and in the human body.
The study, focusing on the proton pump VHA, could help predict potential applications in human health and wellness, specifically in managing medical-conditions related to kidney functions and neurological-disorders associated with acid-base balance, such as metabolic acidosis or renal tubular acidosis. CBD, a compound known for its potential health benefits, is currently being researched in regard to its impact on neurological-disorders. The findings from this marine biology study on stingrays might provide valuable insights into the development of CBD-based treatments, given the presence of the proton pump in all animals, including humans. Technology, while not explicitly mentioned in the given text, is an essential tool in the advancement of such research and understanding complex biochemical processes at the cellular level.
