Cholesterol Inhibits M-type K+ Channels via Protein Kinase C-dependent Phosphorylation in Sympathetic Neurons

Lee, Seul Yi; Choi, Ho Jin; Kim, Seong-Tae; Chung, Sungkwon; Park, Myoung Kyu; Cho, Jung-Hwa; Ho, Won‐Kyung; Cho, Hanna

doi:10.1074/jbc.m109.048868

Cited by 25 publications

(19 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Early stages of PCa growth depends on androgen which also regulate Ca 2+ entry 9-11 , thus, it is very likely that Ca 2+ channels will play an essential role in cellular proliferation and development of PCa 12 . Additionally, cholesterol has been shown to regulate various ion channels 13-15 ; however the Ca 2+ channel(s) involved in cholesterol induced proliferation in prostate cells is not yet identified. Hence, understanding the role of Ca 2+ channels that are regulated by cholesterol and induces cell proliferation and/or migration may lead to a better therapeutic target for PCa.…”

Section: Introductionmentioning

confidence: 99%

Cholesterol-induced activation of TRPM7 regulates cell proliferation, migration, and viability of human prostate cells

Sun

Sukumaran

Varma³

et al. 2014

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

View full text Add to dashboard Cite

Cholesterol has been shown to promote cell proliferation/migration in many cells; however the mechanism(s) have not yet been fully identified. Here we demonstrate that cholesterol increases Ca2+ entry via the TRPM7 channel, which promoted proliferation of prostate cells by inducing activation of the AKT and/or the ERK pathway. Additionally, cholesterol mediated Ca2+ entry induced calpain activity that showed a decrease in E-cadherin expression, which together could lead to migration of prostate cancer cells. Overexpression of TRPM7 significantly facilitated cholesterol dependent Ca2+ entry, cell proliferation and tumor growth. Whereas, TRPM7 silencing or inhibition of cholesterol synthesis by statin showed a significant decrease in cholesterol-mediated activation of TRPM7, cell proliferation, and migration of prostate cancer cells. Consistent with these results, statin intake was inversely correlated with prostate cancer patients and increase in TRPM7 expression was observed in samples obtained from prostate cancer patients. Altogether, we provide evidence that cholesterol-mediated activation of TRPM7 is important for prostate cancer and have identified that TRPM7 could be essential for initiation and/or progression of prostate cancer.

show abstract

Section: Introductionmentioning

confidence: 99%

Cholesterol-induced activation of TRPM7 regulates cell proliferation, migration, and viability of human prostate cells

Sun

Sukumaran

Varma³

et al. 2014

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

View full text Add to dashboard Cite

show abstract

“…The nuclear localization of DGKζ in central and peripheral neurons has been well demonstrated as discussed above. Although no information is so far available about the functional involvement of nuclear DGKζ in neurons, it is worth noticing the previous findings that PKC is involved in the regulation of activation of the transcription factor CREB in the parasympathetic ciliary ganglion (Kamaishi et al 2004;Sumner and Margiotta 2008), in the regulation of various ion channels and receptors through phosphorylation in autonomic as well as central neurons (Heppner and Fiekers 2003;Lee et al 2010;Kim et al 2012), and in angiotensin II-induced inhibition of Ca +2 currents via G(q/11)-protein in the submandibular ganglion . The present finding thus leads us as a next step to examine how the DAG-PKC cascade is involved via DGKζ in the autonomic neuronal function including differentiation and transmission.…”

Section: Discussionmentioning

confidence: 98%

Selective localization of diacylglycerol kinase (DGK)ζ in the terminal tubule cells in the submandibular glands of early postnatal mice

Hipkaeo

Chomphoo

Pakkarato

et al. 2015

Histochem Cell Biol

View full text Add to dashboard Cite

The present immunohistochemical study was attempted to localize in the submandibular glands of mice at various postnatal stages a diacylglycerol kinase (DGK) isoform termed DGKζ which is characterized by a nuclear localization signal and a nuclear export signal. This attempt was based on following facts: the continuous postnatal differentiation of glandular cells in the rodent submandibular gland, the regulatory role of DGK in the activity of protein kinase C (PKC) through attenuation of diacylglycerol (DAG), and the possible involvement of PKC in various cellular activities including the saliva secretion as well as the cell differentiation. As a result, a selective localization of immunoreactivity for DGKζ was detected in terminal tubule (TT) cells which comprise a majority of the newborn acinar structure and differentiate into the intercalated duct cells and/or the acinar cells. The immunoreactivity was deposited in portions of the cytoplasm lateral and basal to the nucleus, but not in the nuclei themselves. Although the immunoreactive TT cells remained until later stages in female specimen than in male, they eventually disappeared in both sexes by young adult stages. The present finding suggests that the regulatory involvement of DGKζ in PKC functions via control of DAG is exerted in the differentiation of the TT cells. In addition, another possible involvement of DGKζ in the regulation of secretion of the TT cells as well as its functional significance of its nuclear localization in the submandibular ganglion cells was also discussed.

show abstract

“…Moreover, cell cycle proteins such as cyclin D1 are targets for antiproliferative agents (7,8). Therefore, in this study we used Chol:MbCD complex (9) to promote VSMC proliferation, an already established cell model from our previous study (10) to investigate the effect of ezetimibe on Chol:MbCD-induced VSMC proliferation and the underlying cellular and molecular mechanisms.…”

Section: Inhibition Of Smooth Muscle Cell Proliferation By Ezetimibe mentioning

confidence: 99%

Inhibition of Smooth Muscle Cell Proliferation by Ezetimibe via the Cyclin D1-MAPK Pathway

Qin

Yang

et al. 2014

J Pharmacol Sci

View full text Add to dashboard Cite

Proliferation of vascular smooth muscle cells (VSMCs) contributes to the development of atherosclerosis. Ezetimibe is a new lipid lowering agent that inhibits cholesterol absorption. In the present study we attempted to investigate whether ezetimibe has any effect on VSMC proliferation and the potential mechanisms involved. Our data showed ezetimibe abrogated the proliferation and migration of primary rat VSMCs induced by Chol:MβCD. Mechanically, we found that ezetimibe was capable of abolishing cyclin D1, CDK2, phospho-Rb (p-Rb), and E2F protein expressions that were upregulated by Chol:MβCD treatment. In addition, Ezetimibe was able to reverse cell cycle progression induced by Chol:MβCD, which was further supported by its down-regulation of cyclin D1 promoter activity in the presence of Chol:MβCD. Furthermore, ezetimibe abrogated the increment of phospho-ERK1/2 (p-ERK1/2) and nuclear accumulation of ERK1/2 in VSMCs induced by Chol:MβCD. Inhibition of the MAPK pathway by using ERK1/2 inhibitor PD98059 attenuated the reduction effect of ezetimibe on the expressions of phosphor-MEK1 (p-MEK1), p-ERK1/2, and cyclin D1. Taken together our data suggest that ezetimibe inhibits Chol:MβCD-induced VSMCs proliferation and leads to cell cycle arrest at the G0/G1 phase by suppressing cyclin D1 expression via the MAPK signaling pathway. These novel findings support the potential pleiotropic effect of ezetimibe in cardiovascular disease.

show abstract

Cholesterol Inhibits M-type K+ Channels via Protein Kinase C-dependent Phosphorylation in Sympathetic Neurons

Cited by 25 publications

References 58 publications

Cholesterol-induced activation of TRPM7 regulates cell proliferation, migration, and viability of human prostate cells

Cholesterol-induced activation of TRPM7 regulates cell proliferation, migration, and viability of human prostate cells

Selective localization of diacylglycerol kinase (DGK)ζ in the terminal tubule cells in the submandibular glands of early postnatal mice

Inhibition of Smooth Muscle Cell Proliferation by Ezetimibe via the Cyclin D1-MAPK Pathway

Contact Info

Product

Resources

About