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Craig T Werner, Michael T Stefanik, Mike Milovanovic, Aaron Caccamise, Marina E Wolf
Exposure to drug-associated cues can induce drug craving and relapse in abstinent addicts. Cue-induced craving that progressively intensifies ("incubates") during withdrawal from cocaine has been observed in both rats and humans. Building on recent evidence that aberrant protein translation underlies incubation-related adaptations in the NAc, we used male rats to test the hypothesis that translation is dysregulated during cocaine withdrawal and/or when rats express incubated cocaine craving. We found that intra-NAc infusion of anisomycin, a general protein translation inhibitor, or rapamycin, an inhibitor of mammalian target of rapamycin, reduced the expression of incubated cocaine craving, consistent with previous results showing that inhibition of translation in slices normalized the adaptations that maintain incubation...
March 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Sung-Min Ju, Yong-Seok Jo, Yoo-Min Jeon, Hyun-Ock Pae, Dae-Gill Kang, Ho-Sub Lee, Jun-Sang Bae, Byung-Hun Jeon
Cisplatin is one of the most widely used chemotherapeutic agents for the treatment of human cancers. However, the nephrotoxicity of cisplatin limits its use as a therapeutic agent. It has been suggested that oxidative stress and p53 activation play important roles in cisplatin-induced nephrotoxicity. It has been demonstrated that the eukaryotic translation initiation factor 2α (eIF2α) may protect HK-2 human renal proximal tubular cells against cisplatin-induced apoptosis through inhibition of reactive oxygen species (ROS)‑mediated p53 activation...
October 10, 2017: International Journal of Molecular Medicine
Min Jian, Yi-Xiao Luo, Yan-Xue Xue, Ying Han, Hai-Shui Shi, Jian-Feng Liu, Wei Yan, Ping Wu, Shi-Qiu Meng, Jia-Hui Deng, Hao-Wei Shen, Jie Shi, Lin Lu
Maladaptive memories elicited by exposure to environmental stimuli associated with drugs of abuse are often responsible for relapse among addicts. Interference with the reconsolidation of drug memory can inhibit drug seeking. Previous studies have indicated that the dephosphorylation of the eukaryotic initiation factor 2 α-subunit (eIF2α) plays an important role in synaptic plasticity and long-term memory consolidation, but its role in the reconsolidation of drug memory remains unknown. The amygdala is required for the reconsolidation of a destabilized drug memory after retrieval of drug-paired stimuli...
July 23, 2014: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Kinnosuke Yahiro, Hiroyasu Tsutsuki, Kohei Ogura, Sayaka Nagasawa, Joel Moss, Masatoshi Noda
Shiga-toxigenic Escherichia coli (STEC) produces subtilase cytotoxin (SubAB), which cleaves the molecular chaperone BiP in the endoplasmic reticulum (ER), leading to an ER stress response and then activation of apoptotic signaling pathways. Here, we show that an early event in SubAB-induced apoptosis in HeLa cells is mediated by RNA-dependent protein kinase (PKR)-like ER kinase (PERK), not activating transcription factor 6 (ATF6) or inositol-requiring enzyme 1(Ire1), two other ER stress sensors. PERK knockdown suppressed SubAB-induced eIF2α phosphorylation, activating transcription factor 4 (ATF4) expression, caspase activation, and cytotoxicity...
May 2012: Infection and Immunity
Mauro Costa-Mattioli, Delphine Gobert, Elad Stern, Karine Gamache, Rodney Colina, Claudio Cuello, Wayne Sossin, Randal Kaufman, Jerry Pelletier, Kobi Rosenblum, Kresimir Krnjević, Jean-Claude Lacaille, Karim Nader, Nahum Sonenberg
The late phase of long-term potentiation (LTP) and memory (LTM) requires new gene expression, but the molecular mechanisms that underlie these processes are not fully understood. Phosphorylation of eIF2alpha inhibits general translation but selectively stimulates translation of ATF4, a repressor of CREB-mediated late-LTP (L-LTP) and LTM. We used a pharmacogenetic bidirectional approach to examine the role of eIF2alpha phosphorylation in synaptic plasticity and behavioral learning. We show that in eIF2alpha(+/S51A) mice, in which eIF2alpha phosphorylation is reduced, the threshold for eliciting L-LTP in hippocampal slices is lowered, and memory is enhanced...
April 6, 2007: Cell
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