Abstract
CYP2B proteins in rat hepatocytes undergo NO-dependent proteolytic degradation, but the mechanisms and the reasons for the specificity towards only certain P450 (cytochrome P450) enzymes are yet unknown. In the present study we found that down-regulation of CYP2B proteins by the NO donor NOC-18 is accelerated by pretreatment of the hepatocytes with IL-1 (interleukin-1β) in the presence of an NO synthase inhibitor, suggesting that an NO-independent action of IL-1 contributes to the lability of CYP2B proteins. The immunoproteasome subunit LMP2 (large multifunctional peptidase 2) was significantly expressed in hepatocytes under basal conditions, and IL-1 induced LMP2 within 6-12 h of treatment. CYP2B protein degradation in response to IL-1 was attenuated by the selective LMP2 inhibitor UK-101, but not by the LMP7 inhibitor IPSI. The results showthat LMP2 contributes to the NO-dependent degradation of CYP2B proteins, and suggest that induction of LMP2 may be involved in the potentiation of this degradation by IL-1.
Original language | English |
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Pages (from-to) | 377-382 |
Number of pages | 6 |
Journal | Biochemical Journal |
Volume | 445 |
Issue number | 3 |
DOIs | |
State | Published - Aug 1 2012 |
Keywords
- Cytochrome P450
- Immunoproteasome
- Interleukin-1 (IL-1)
- Nitric oxide (NO)
- Proteasome
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology