Role of Calcium Sensing Receptor in Streptozotocin-Induced Diabetic Rats Exposed to Renal Ischemia Reperfusion Injury

Abstract

Background/Aims: Renal ischemia/reperfusion (I/R) injury (RI/RI) is a common complication of diabetes, and it may be involved in altering intracellular calcium concentrations at its onset, which can result in inflammation, abnormal lipid metabolism, the production of reactive oxygen species (ROS), and nitroso-redox imbalance. The calcium-sensing receptor (CaSR) is a G-protein coupled receptor, however, the functional involvement of CaSR in diabetic RI/ RI remains unclear. The present study was intended to investigate the role of CaSR on RI/RI in diabetes mellitus (DM). Methods: The bilateral renal arteries and veins of streptozotocin (STZ)-induced diabetic rats were subjected to 45-min ischemia followed by 2-h reperfusion with or without R-568 (agonist of CaSR) and NPS-2143 (antagonist of CaSR) at the beginning of I/R procedure. DM without renal I/R rats served as control group. The expressions of CaSR, calmodulin (CaM), and p47phox in the renal tissue were analyzed by qRT-PCR and Western blot. The renal pathomorphology, renal function, oxidative stress, inflammatory response, and calcium disorder were evaluated by detection of a series of indices by hematoxylin-eosin (HE) staining, transmission electron microscope (TEM), commercial kits, enzyme-linked immunosorbent assay (ELISA), and spectrophotofluorometry, respectively. Results: Results showed that the expressions of CaSR, CaM, and p47phox in I/R group were significantly up-regulated as compared with those in DM group, which were accompanied by renal tissue injury, increased calcium, oxidative stress, inflammation, and nitroso-redox imbalance. Conclusion: These results suggest that activation of CaSR is involved in the induction of damage of renal tubular epithelial cell during diabetic RI/RI, resulting in lipid peroxidation, inflammatory response, nitroso-redox imbalance, and apoptosis.

Astragaloside IV attenuates cerebral ischemia‑reperfusion injury in rats through the inhibition of calcium‑sensing receptor‑mediated apoptosis

“…caSR maintains calcium homeostasis, and its activity serves an important role in increased intracellular calcium levels during I/R injury (17,25,26). Previous studies have reported that the activation of caSR aggravates myocardial and renal I/R injury and mouse cIRI (19,23,27,28). However, it remains unclear whether increased caSR expression may induce apoptosis by increasing intracellular calcium overload during cIRI, and whether Astragaloside IV may reduce caSR expression to alleviate intracellular calcium overload and further inhibit cIRI-induced apoptosis.…”

“…Based on our previous study, rats in the AST-IV group were intraperitoneally injected with 20 mg/kg Astragaloside IV during reperfusion (9). Rats in the NPS-2143 group were intraperitoneally injected with 10 µmol/kg NPS-2143 during reperfusion (23,24,28), and rats in the Sham group received an equal volume of physiological saline. Room temperature was maintained at 28-32˚C throughout the surgery.…”

Apocynin Attenuates Cobalt Chloride-Induced Pheochromocytoma Cell Apoptosis by Inhibiting P38-MAPK/Caspase-3 Pathway

“…The primers sequences were shown in Table 1. Relative mRNA expression levels of p38MAPK and caspase-3 were calculated using the 2 -ΔΔCt method after normalization to the expression of GAPDH [16,17].…”

Ethylenediaminetetraacetic Acid Inhibits <b><i>Vibrio Vulnificus</i></b>-Induced Dendritic Cell Apoptosis by Lowering [Ca²⁺]_i

“…The western blotting analysis was performed as previously described [14,15]. Briefly, an equal amount of proteins was loaded and fractionated on 10% sodium dodecyl sulfate-polyacrylamide gels (SDS-PAGE) and transferred to the polyvinylidene fluoride (PVDF) membrane (Millipore, MA).…”