{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T14:09:18Z","timestamp":1773238158852,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,6,22]],"date-time":"2012-06-22T00:00:00Z","timestamp":1340323200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:sec><jats:label\/><jats:p><jats:italic>J. Neurochem.<\/jats:italic> (2012) <jats:bold>122<\/jats:bold>, 487\u2013500.<\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Genetic deletion or mutations of presenilin genes (PS1\/PS2) cause familial Alzheimer\u2019s disease and calcium (Ca<jats:sup>2+<\/jats:sup>) signaling abnormalities. PS1\/PS2 act as endoplasmic reticulum (ER) Ca<jats:sup>2+<\/jats:sup> leak channels that facilitate passive Ca<jats:sup>2+<\/jats:sup> leak across ER membrane. Studies with PS1\/PS2 double knockout (PS1\/PS2\u2010DKO) mouse embryonic fibroblasts showed that PS1\/PS2 were responsible for 80% of passive Ca<jats:sup>2+<\/jats:sup> leak from the lumen of endoplasmic reticulum to cytosol. Transient transfection of the wild type PS1 expression construct increased cytoplasmic Ca<jats:sup>2+<\/jats:sup> as a result of Ca<jats:sup>2+<\/jats:sup> leak across ER membrane whereas the FADPS1 (PS1\u2010M146V) mutation construct alone or in combination with the wild type PS1 expression construct abrogated Ca<jats:sup>2+<\/jats:sup> leak in SK\u2010N\u2010SH cells. Inhibition of basal c\u2010jun\u2010NH2\u2010terminal kinase (JNK) activity by JNK inhibitor SP600125 repressed PS1 transcription and PS1 protein expression by augmenting p53 protein level in SK\u2010N\u2010SH cells (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"#b9\">Lee and Das 2008<\/jats:ext-link>). In this report we also showed that repression of PS1 transcription by JNK inhibitor SP600125 inhibited passive Ca<jats:sup>2+<\/jats:sup> leak across ER membrane which could be rescued by expressing PS1 wild type and not by expressing FADPS1 (PS1\u2010M146V) under a SP600125 non\u2010responsive promoter. Treatment of SK\u2010N\u2010SH cells with SP600125 also triggered InsP3R\u2010mediated Ca<jats:sup>2+<\/jats:sup> release from the ER by addition of 500\u2003nM bradykinin, an agonist of InsP3 receptor (InsP3R1) without changing the expression of InsP3R1. This data confirms that SP600125 increases the Ca<jats:sup>2+<\/jats:sup> store in the ER by inhibiting PS1\u2010mediated Ca<jats:sup>2+<\/jats:sup> leak across ER membrane. p53, ZNF237 and Chromodomain helicase DNA\u2010binding protein 3 which are repressors of PS1 transcription, also reduced Ca<jats:sup>2+<\/jats:sup> leak across ER membrane in SK\u2010N\u2010SH cells but \u03b3\u2010secretase inhibitor or dominant negative \u03b3\u2010secretase\u2013specific PS1 mutant (PS1\u2010D257A) had no significant effect. Therefore, p53, ZNF237, and Chromodomain helicase DNA\u2010binding protein 3 inhibit the function ER Ca<jats:sup>2+<\/jats:sup> leak channels to regulate both ER and cytoplasmic Ca<jats:sup>2+<\/jats:sup> levels and may potentially control Ca<jats:sup>2+<\/jats:sup>\u2010signaling function of PS1.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1471-4159.2012.07794.x","type":"journal-article","created":{"date-parts":[[2012,5,21]],"date-time":"2012-05-21T10:56:00Z","timestamp":1337597760000},"page":"487-500","source":"Crossref","is-referenced-by-count":18,"title":["Repression of transcription of presenilin\u20101 inhibits \u03b3\u2010secretase independent ER Ca<sup>2+<\/sup> leak that is impaired by FAD mutations"],"prefix":"10.1111","volume":"122","author":[{"given":"Hriday K.","family":"Das","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kissaou","family":"Tchedre","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brett","family":"Mueller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,6,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.2.567"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80230-5"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.1.43"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.52.30853"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/349704a0"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)83641-4"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072994"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/35017105"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2008.02.016"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.2741\/e61"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-23-07513.1996"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110371200"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.072033799"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7638622"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/35015085"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M007340200"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.34.24297"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M005411200"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2006.10.056"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2007.05684.x"},{"key":"e_1_2_7_22_1","first-page":"1142","article-title":"Cholinergic and adrenergic modulation of the Ca2+ response to endothelin\u20101 in human ciliary muscle cells","volume":"41","author":"Prasanna G.","year":"2000","journal-title":"Invest. 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