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We recently established a role for <jats:styled-content style=\"fixed-case\">NMDA<\/jats:styled-content> receptor\u2010mediated activation of extracellular signal\u2010regulated kinase (<jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>)\u2010<jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content> in homocysteine\u2010induced neuronal cell death. In this study, we examined the involvement of the stress\u2010induced <jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content>, p38 in homocysteine\u2010induced neuronal cell death, and further explored the relationship between the two <jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content>s, <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content> and p38, in triggering cell death. Homocysteine\u2010mediated <jats:styled-content style=\"fixed-case\">NMDA<\/jats:styled-content> receptor stimulation and subsequent Ca<jats:sup>2+<\/jats:sup> influx led to a biphasic activation of p38 <jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content> characterized by an initial rapid, but transient activation followed by a delayed and more prolonged response. Selective inhibition of the delayed p38 <jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content> activity was sufficient to attenuate homocysteine\u2010induced neuronal cell death. Using pharmacological and <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>i approaches, we further demonstrated that both the initial and delayed activation of p38 <jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content> is downstream of, and dependent on activation of <jats:styled-content style=\"fixed-case\">ERK MAPK<\/jats:styled-content>. Our findings highlight a novel interplay between <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content> and p38 <jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content> in homocysteine\u2010<jats:styled-content style=\"fixed-case\">NMDA<\/jats:styled-content> receptor\u2010induced neuronal cell death.<\/jats:p>","DOI":"10.1111\/jnc.12102","type":"journal-article","created":{"date-parts":[[2012,11,24]],"date-time":"2012-11-24T08:04:10Z","timestamp":1353744250000},"page":"558-570","source":"Crossref","is-referenced-by-count":58,"title":["Novel crosstalk between <scp>ERK MAPK<\/scp> and p38 <scp>MAPK<\/scp> leads to homocysteine\u2010<scp>NMDA<\/scp> receptor\u2010mediated neuronal cell death"],"prefix":"10.1111","volume":"124","author":[{"given":"Ranjana","family":"Poddar","sequence":"first","affiliation":[{"name":"University of New Mexico Health Sciences Center Department of Neurology 1, University of New Mexico Albuquerque NM USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surojit","family":"Paul","sequence":"additional","affiliation":[{"name":"University of New Mexico Health Sciences Center Department of Neurology 1, University of New Mexico Albuquerque NM USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,12,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.46.27489"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/156802606777323700"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90098-J"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M003390200"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2008.10.029"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M311164200"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3260001"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20100323"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1012541011123"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3510095"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0022-3042.2001.00676.x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)00129-X"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.29.18623"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-6870"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11-7256"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn835"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.2174\/156802606777057553"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.10416"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2001.281.4.C1266"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03033381"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-7859rev"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.01154.2006"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.04.031"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.08.003"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-18-06920.2000"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-05-01752.2002"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(02)01890-3"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn912"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.11.5923"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0116-07.2007"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702373200"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2004.03223.x"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(03)00032-8"},{"key":"e_1_2_7_35_1","first-page":"126","article-title":"Homocysteine and Alzheimer's disease","volume":"57","author":"Miller J. 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