Nicotine coregulates multiple pathways involved in protein modification/degradation in rat brain
Abstract
Previously, we used cDNA microarrays to demonstrate that the phosphatidylinositol and MAP kinase signaling pathways are regulated by nicotine in different rat brain regions. In the present report, we show that, after exposure to nicotine for 14 days, ubiquitin, ubiquitin-conjugating enzymes, 20S and 19S proteasomal subunits, and chaperonin-containing TCP-1 protein (CCT) complex members are upregulated in rat prefrontal cortex (PFC) while being downregulated in the medial basal hypothalamus (MBH). In particular, relative to saline controls, ubiquitins B and C were upregulated by 33% and 47% (P<0.01), respectively, in the PFC. The proteasome beta subunit 1 (PSMB1) and 26S ATPase 3 (PSMC3) genes were upregulated in the PFC by 95% and 119% (P<0.001), respectively. In addition to the protein degradation pathway of the ubiquitin-proteasome complexes, we observed in the PFC an increase in the expression of small, ubiquitin-related modifiers (SUMO) 1 and 2 by 80% and 33%, respectively (P<0.001), and in 3 of 6 CCT subunits by up to 150% (P<0.0001). To a lesser extent, a change in the opposite direction was obtained in the expression of the same gene families in the MBH. Quantitative real-time RT-PCR was used to validate the microarray results obtained with some representative genes involved in these pathways. Taken together, our results suggest that, in response to systemic nicotine administration, the ubiquitin-proteasome, SUMO, and chaperonin complexes provide an intricate control mechanism to maintain cellular homeostasis, possibly by regulating the composition and signaling of target neurons in a region-specific manner.
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Upregulation of α4β2 nAChRs may involve increased receptor protein through post-translational events, possibly including changes in nAChR maturation and trafficking.
“Thus, upregulation of α4β2 nAChRs may involve an increase in receptor protein through post-translational events that may include changes in nAChR maturation and trafficking (Darsow et al., 2005; Kane et al., 2004; Lomazzo et al., 2011; Rezvani et al., 2007).”
From The duration of nicotine withdrawal-associated deficits in contextual fear conditioning parallels changes in hippocampal high affinity nicotinic acetylcholine receptor upregulation (2012) · cites this paper as Kane et al., 2004
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“Thus, upregulation of a4b2 nAChRs may involve an increase in receptor protein through posttranslational events that may include changes in nAChR maturation and trafficking (Darsow et al., 2005; Kane et al., 2004; Lomazzo et al., 2011; Rezvani et al., 2007).”
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- Authors
- Kane, J. K., Konu, Ö., Ma, J. Z., & Li, M. D.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Bilkent University (TR)
- Corresponding author
- Li, Ming D.
- Venue
- Molecular Brain Research
- Publisher
- Elsevier BV
- Published
- 2004-12
- Volume
- 132
- Issue
- 2
- Pages
- 181-191
- ISSN
- 0169-328X (ISSN-L)
- OpenAlex
- W1980060298
- Cited by
- 61
- References
- 62
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 4 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 2 · 2014: 3 · 2013: 3 · 2012: 3
- FWCI
- 1.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Bilkent University Institutional Repository (Bilkent University) (submittedVersion)
- Funders
- National Institute on Drug Abuse (DA12844, R01DA012844, R01DA013783, R01 DA 13783)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- nicotine, ubiquitin-proteasome system, protein degradation, small ubiquitin-related modifier, SUMOylation, proteasome, prefrontal cortex, medial basal hypothalamus, regional gene expression, brain homeostasis
- MeSH terms
- Animals, Brain Chemistry, Male, Nicotine, Up-Regulation, Gene Expression, Rats, Sprague-Dawley, Nicotinic Agonists, Chaperonins, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Ubiquitin, SUMO-1 Protein, Proteasome Endopeptidase Complex, Rats
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