Archival ReportE3 Ubiquitin-Protein Ligase SMURF1 in the Nucleus Accumbens Mediates Cocaine Seeking
Section snippets
Subjects
Adult male Sprague Dawley rats (250–275 g; Envigo, Indianapolis, IN) were singly housed on a reverse light/dark cycle and had ad libitum access to food and water. This study was conducted in accordance with the guidelines set up by the Institutional Animal Care and Use Committee of The State University of New York at Buffalo.
Drugs
Cocaine hydrochloride, gifted by the National Institute on Drug Abuse (Bethesda, MD), was dissolved in sterile 0.9% saline (4.5 mg/mL). Pump durations/injection volumes
SMURF1 Is Decreased in the NAc in a Withdrawal-Dependent Manner Following Cocaine Self-administration
RhoA and the TGF-β superfamily have previously been implicated in cocaine-dependent plasticity 22, 23, 24, 25, 26, 32, 33. We therefore set out to determine whether SMURF1, which regulates RhoA and BMP signal transducers SMAD1 and SMAD5, is involved in cocaine-related cellular and behavioral plasticity. To do so, we first asked whether SMURF1 and substrates are altered after cocaine exposure. Rats were trained to nose poke to receive intravenous infusions of saline or cocaine paired with a
Discussion
Long-term neuroadaptations in brain regions that process reward and motivation, including the NAc, underlie relapse vulnerability. The UPS governs activity-dependent synaptic plasticity 5, 6, 64, 65 and has been shown to be involved in cocaine-related plasticity in the NAc 15, 16, 66, 67. However, E3s, which mediate polyubiquitination of substrates for proteasomal degradation, have not been examined in substance use disorder. In this study, we examined the E3 SMURF1 in cellular and behavioral
Acknowledgments and Disclosures
This work was supported by the National Institutes of Health (National Institute on Drug Abuse [NIDA] Grant No. R01DA037257 [to DMD], Grant No. S1-R01DA037257 [to DMD], NIDA Grant No. R21DA044486 [to DMD], National Institute of Neurological Disorders and Stroke Grant No. F99NS108543 [to JAM], and National Institute of General Medical Sciences Grant No. R25GM09545902 [to University at Buffalo]). The NIDA Drug Supply Program generously gifted the cocaine used in these studies.
CTW, RV, J-XL, and
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2023, Pharmacology Biochemistry and BehaviorThe ubiquitin-proteasome system and learning-dependent synaptic plasticity – A 10 year update
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2020, Neurobiology of Learning and MemoryCitation Excerpt :Furthermore, recent evidence suggests that protein degradation is a critical regulator of memory formation and stability. Within cells of multiple brain regions, learning increases the amount of degradation-specific polyubiquitination and proteasome catalytic activity and administration of catalytic inhibitors of the proteasome result in memory impairments for a variety of behavioral tasks (Artinian et al., 2008; Cullen, Ferrara, Pullins, & Helmstetter, 2017; Figueiredo et al., 2015; Jarome, Werner, Kwapis, & Helmstetter, 2011; Lopez-Salon et al., 2001; Reis, Jarome, & Helmstetter, 2013; Rodriguez-Ortiz, Balderas, Saucedo-Alquicira, Cruz-Castaneda, & Bermudez-Rattoni, 2011) and disease models, such as drug addiction (Werner et al., 2019; Werner et al., 2018). Furthermore, protein degradation has been shown to control the destabilization of memory after retrieval, suggesting a critical role for it in the reconsolidation process (Ferrara et al., 2019; Jarome et al., 2011; Lee, 2008; Lee et al., 2008), and has been widely implicated in the reconsolidation of drug-associated behaviors (Massaly et al., 2013; Werner, Milovanovic, Christian, Loweth, & Wolf, 2015).
Glucose fluctuations promote vascular BK channels dysfunction via PKCα/NF-κB/MuRF1 signaling
2020, Journal of Molecular and Cellular CardiologyCitation Excerpt :IκB kinase (IKK) promotes the phosphorylation of IκB, enabling IκB to dissociate from p65 [11]. The muscle ring finger protein 1 (MuRF1) is a target gene regulated by NF-κB in diabetic vascular SMCs [12]. MuRF1 is known as a muscle specific E3 ligase and plays an important role in the downregulation of BK-β1 subunits in diabetic mouse arteries [13].
Sex-Specific Role for Egr3 in Nucleus Accumbens D2-Medium Spiny Neurons Following Long-Term Abstinence From Cocaine Self-administration
2020, Biological PsychiatryCitation Excerpt :Mice received a bilateral NAc (from bregma: anteroposterior: +1.6, mediolateral: +/−1.5, dorsoventral: −4.4; 10° angle) injection of a Cre-inducible, double inverted open (DIO)-reading frame adeno-associated virus (AAV) AAV-DIO-Egr3-eYFP or AAV-DIO-eYFP under light isoflurane anesthesia as previously described (6,19,20). Following rapid decapitation, brains were removed and sliced into 1-mm-thick sections, and tissue punches targeting the NAc were collected for immunoblotting as described elsewhere (14,21,22). Tissue was homogenized in 30 μL of homogenization buffer (320 mM sucrose, 5 mM HEPES buffer, 1% sodium dodecyl sulfate [SDS]), phosphatase inhibitor cocktails 2 and 3 (Sigma-Aldrich, St. Louis, MO), and protease inhibitors (Roche, Basel, Switzerland).
Research Progress in Function and Regulation of E3 Ubiquitin Ligase SMURF1
2023, Current Medical Science
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CTW and RV contributed equally to this work.