LAUSR

Zinc, the second most abundant divalent cation in the human body, is a fundamental microelement involved in regulating many cellular and subcellular functions. Abnormalities of zinc homeostasis are frequent in patients with Chronic Kidney Disease (CKD). Multiple clinical studies reported lower plasma zinc levels and higher urinary zinc excretion in patients with type 2 diabetes and CKD. Experimental studies reported that zinc may be involved in renal damage and could contribute to blood pressure (BP) regulation.We hypothesize that increased levels of zinc during the development of CKD could mediate intracellular signaling leading to cell damage in different parts of the nephron. To define intracellular calcium ([Ca2+]i) changes, we loaded immortalized human podocyte and mouse cortical collecting duct (mCCD) cells with Fluo-4 calcium dye. Experiments with Zn2+ application (100 uM) in podocytes revealed a fast transient calcium response (1450 ± 142 a.u., maximum calcium response, n≥55 cells). In mCCD cells, Zn2+ application did not promote [Ca2+]i changes. It was reported that [Ca2+]i overload in podocytes could lead to cell damage and death. To test whether Zn2+ induces cell apoptosis, we used a fluorescent indicator for measuring caspase 3/7 activation in live immortalized human podocytes cells. Incubation podocytes with high concentrations of Zn2+ (200 μM) resulted in higher caspase 3/7 activation after 48 hours compared to the control. Furthermore, we used the Zn2+-selective fluorescence indicator FluoZin-3 to determine intracellular Zn2+ changes. In podocytes, Zn2+ application (100 uM) did not cause changes in intracellular Zn2+ levels, but in mCCD, there was a fast sustained zinc response (2550 ± 864 a.u., maximum zinc response, n≥60 cells).The presence of Zn2+ signaling in mCCD cells could be involved in BP regulation since CCD cells play an important role in Na+ handling and subsequent BP regulation. Here, we decided to characterize the effect of zinc on the development of salt-induced hypertension and kidney function in vivo. Dahl Salt-Sensitive (SS) rats were fed with zinc-deficient (5 ppm) or zinc-supplementary (180 ppm) high-salt diets. We found that neither a deficient nor supplementary diet did affect BP assessed with telemetry compared to the control group. Also, no changes were observed in diuresis, as well as in kidney, heart, and body weight. Despite the lack of effect of zinc on the development of salt-induced hypertension, the prominent involvement of zinc in calcium homeostasis and apoptosis in podocytes and the presence of zinc level changes in mCCD cells suggest the importance of zinc in kidney homeostasis under normal and pathological conditions. Thus, further studies are needed to clarify the underlying mechanisms and the potential role of zinc in CKD and BP development. This research was supported by NIH grant R35 HL135749 (to AS) and APS Postdoctoral Fellowship (to RB). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.