RGD Reference Report - High glucose alters apoptosis and proliferation in HEK293 cells by inhibition of cloned BK Ca channel. - Rat Genome Database

RGD Reference Report - High glucose alters apoptosis and proliferation in HEK293 cells by inhibition of cloned BK Ca channel. - Rat Genome Database

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High glucose alters apoptosis and proliferation in HEK293 cells by inhibition of cloned BK Ca channel.
Authors:	Chang, H Ma, YG Wang, YY Song, Z Li, Q Yang, N Zhao, HZ Feng, HZ Chang, YM Ma, J Yu, ZB Xie, MJ
Citation:	Chang H, etal., J Cell Physiol. 2011 Jun;226(6):1660-75. doi: 10.1002/jcp.22497.
RGD ID:	10412040
Pubmed:	PMID:21413024 (View Abstract at PubMed)
DOI:	DOI:10.1002/jcp.22497 (Journal Full-text)
It has been reported that diabetic vascular dysfunction is associated with impaired function of large conductance Ca(2+) -activated K(+) (BK(Ca) ) channels. However, it is unclear whether impaired BK(Ca) channel directly participates in regulating diabetic vascular remodeling by altering cell growth in response to hyperglycemia. In the present study, we investigated the specific role of BK(Ca) channel in controlling apoptosis and proliferation under high glucose concentration (25 mM). The cDNA encoding the alpha+beta1 subunit of BK(Ca) channel, hSloalpha+beta1, was transiently transfected into human embryonic kidney 293 (HEK293) cells. Cloned BK(Ca) currents were recorded by both whole-cell and cell-attached patch clamp techniques. Cell apoptosis was assessed with immunocytochemistry and analysis of fragmented DNA by agarose gel electrophoresis. Cell proliferation was investigated by flow cytometry assays, MTT test, and immunocytochemistry. In addition, the expression of anti-apoptotic protein Bcl-2, intracellular Ca(2+) , and mitochondrial membrane potential (Deltapsim) were also examined to investigate the possible mechanisms. Our results indicate that inhibition of cloned BK(Ca) channels might be responsible for hyperglycemia-altered apoptosis and proliferation in HEK-hSloalpha+beta1 cells. However, activation of BK(Ca) channel by NS1619 or Tamoxifen significantly induced apoptosis and suppressed proliferation in HEK-hSloalpha+beta1 cells under hyperglycemia condition. When rat cerebral smooth muscle cells were cultured in hyperglycemia, similar findings were observed. Moreover, the possible mechanisms underlying the activation of BK(Ca) channel were associated with decreased expression of Bcl-2, elevation of intracellular Ca(2+) , and a concomitant depolarization of Deltapsim in HEK-hSloalpha+beta1 cells. In conclusion, cloned BK(Ca) channel directly regulated apoptosis and proliferation of HEK293 cell under hyperglycemia condition.

Objects referenced in this article

Gene	Kcnmb1	potassium calcium-activated channel subfamily M regulatory beta subunit 1	Rattus norvegicus

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