Attenuated store-operated Ca2+ entry in mesangial cells of aged rat:the role of TRPC1,STIM1 and Orai

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  Store-operated calcium entry (SOCE) is mediated through the specific plasma membrane channels in response to the depletion of Ca2+ from intracellular Ca2+ stores.TRPC1, STIM1 and Orail may involve in this process.Glomerular mesangial cells are contractile cells and located within glomerular capillary loops to regulate the filtration surface area, intraglomerular blood volume, and glomerular filtration rate (GFR).Ca2+ influx is a major response of the mesangial cells toward hormoncs, leading to contraction to regulate GFR.In this study, we investigated the SOCE in the primary cultured mesangial cells of aged (18 months) and young (2 months) rats, and the expression levels of TRPC1, STIM1 and Orail of the fresh-isolated glomeruli from both aged and young rats.Ca2+ stores of the mesangial cells were depleted by thapsigargin, which is an intracellular Ca2+ pump inhibitor.Intracellular Ca2+ ([Ca2+]i) measurement showed that the SOCE of the mesangial cells is significantly attenuated in aged rats (F1/F0:3.77 ± 0.51 vs 8.46 ± 0.92).Immunoblot and immunofluorescence data indicated that TRPC1, STIM1 and Orail expression levels of mesangial cells markedly decreased in aged rats.Transfection of the specific siRNAs for TRPC1, STIM1 or Orai l into the mesangial cells of young rats suppressed the protein expression levels and SOCE.We conclude that the SOCE is attenuated in the mesangial cells of aged rats probably because the expression levels of TRPC 1, STIM 1 or Orai 1 is decreased.
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