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Ischemic preconditioning‐induced cardioprotection is lost in mice with immunoproteasome subunit low molecular mass polypeptide‐2 deficiency
Author(s) -
Cai Zheqing P.,
Shen Zhenyun,
Van Kaer Luc,
Becker Lewis C.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.08-105940
Subject(s) - pten , cardioprotection , tensin , knockout mouse , phosphatase , proteasome , chemistry , protein kinase b , protein subunit , kinase , ischemia , proteolysis , phosphorylation , endocrinology , medicine , signal transduction , biology , pi3k/akt/mtor pathway , biochemistry , enzyme , receptor , gene
The ubiquitin‐proteasome system plays an important role in many cellular processes through degradation of specific proteins. Low molecular mass polypeptide 2 (LMP‐2 or β 1i ) is one important subunit of the immunoproteasome. Ischemic preconditioning (IPC) activates cell signaling pathways and generates cardioprotection but has not been linked to LMP‐2 function previously. LMP‐2 knockout mice (C57BL6 background) and wild‐type C57BL6 mice were sub jected to 30 min of ischemia (I‐30) and 120 min of reperfusion (R‐120) with or without preceding IPC (10 min of infusion and 5 min of reperfusion). IPC signif icantly increased left ventricular developed pressure and decreased infarct size in wild‐type mice, but this protective effect of IPC was lost in LMP‐2 knockout mice. IPC‐mediated degradation of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and activation of the downstream protein kinase Akt were impaired in LMP‐2 knockout hearts. The impair ment of PTEN degradation was associated with defec tive immunoproteasomes and decreased proteolytic activities. When LMP‐2 knockout mice were pretreated with the PTEN inhibitor bpV(HOpic), cardiac function was significantly improved, and myocardial infarct size was significantly reduced after I‐30/R‐120. In conclu sion, LMP‐2 is required for normal proteasomal func tion and IPC induction in the heart. Its action may be related to PTEN protein degradation.— Cai, Z. P., Shen, Z., Van Kaer, L., Becker, L. C. Ischemic preconditioning‐induced cardioprotection is lost in mice with immunoproteasome subunit low molecular mass polypeptide‐2 deficiency. FASEB J. 22, 4248–4257 (2008)