Alterations of Cullin-5 mRNA levels in the rat central nervous system following hemorrhagic shock

Abstract

Hemorrhagic shock is a clinical syndrome that manifests as hypoperfusion, hypoxia, and ischemia initiating various cellular stress responses involved in the synthesis and release of an assortment of pro-inflammatory molecules, cytokines, chemokines, and reactive oxidant species (ROS). The ROS have been shown to oxidize and damage proteins making them targets for ubiquitination and proteasomal degradation. Cullin-5 (cul-5), an E3 ligase that binds ubiquitin to proteins targeted for degradation via the proteasome, was investigated for its gene expression during hemorrhagic shock. Male Long-Evans rats were subjected to volume controlled (27 ml kg-1) hemorrhage over 10 min and kept in shock for 60 min. Quantitative realtime polymerase chain reaction showed cul-5 mRNA levels were significantly increased in the brainstem and cerebellum, and decreased in the hypothalamus of rats as a result of hemorrhagic shock (n = 6) compared to sham-treated rats (n = 6). Cul-5 mRNA levels in the cerebral cortex, small intestine, kidney, liver, lung, or pituitary gland did not significantly change after hemorrhagic shock. This is the first report of cul-5 mRNA regulation by hemorrhagic shock. Evidence indicates this protein may have a regulatory role in ubiquitin-proteasomal protein degradation in response to hemorrhagic shock.

Granulocytic differentiation of HL-60 promyelocytic leukemia cells is associated with increased expression of Cul5

“…A 1.6-fold change in Cul5 mRNA expression, and a 6.5-fold change in Cul5 protein expression, may have an important role in cellular processes such as differentiation since a previous study indicated that a less than twofold increase in the expression of another cullin family member, Cul4A, promotes proliferation and attenuates granulocytic differentiation of the PLB-985 human myeloid leukemia cell line . Other studies have shown similar fold changes in Cul5 expression in some rat tissues following hemorrhagic shock, traumatic brain injury, and osmotic stress (Ceremuga et al 2003a, b;Yao et al 2006). It is also of interest that a recent study showed a decrease in Cul5 mRNA expression in B-cell chronic lymphocytic leukemia (Kalla et al 2007).…”

Cerebral Hypoperfusion Increases Estrogen Receptor Abundance in the Ovine Fetal Brain and Pituitary

“…ER-α is ubiquitinated and degraded in the proteasome [28, 29]. Cerebral ischemia is known to alter proteasomal activity [30, 31], suggesting the possibility that changes in the rate of receptor degradation might alter the concentration of receptor protein relative to receptor mRNA in the hours following BCO. At the mRNA level, ER-α mRNA is rapidly degraded [32]; the rate of degradation is influenced by binding of RNA-binding proteins to 3′ terminal AU-rich regions [33].…”

Hemorrhage and Subsequent Allogenic Red Blood Cell Transfusion are Associated With Characteristic Monocyte Messenger RNA Expression Patterns in Patients After Multiple Injury—A Genome Wide View

“…This is especially evocative, as extracellular ubiquitin and elements of the ubiquitin signaling pathway 28 are not only known to be enhanced in patients after multiple injuries in general, 29 but—if applied for therapeutic reasons—seem to reduce fluid requirements in a experimental hemorrhage mouse model. 30 Furthermore, extracellular ubiquitin seems to have antiinflammatory properties and may be involved in immunosuppressive mechanisms in critical ill patients.…”