In a previous study of a t(4;16)(q26;p13) translocation, found in a human malignant T-cell lymphoma the BCMA gene, located on chromosome band 16p13.1, has been characterized. In this study we show that the BCMA gene is organized into three exons and its major initiation transcription site is located 69 nucleotides downstream of a TATA box. RNase protection assays demonstrated that the BCMA gene is preferentially expressed in mature B cells, suggesting a role for this gene in the B-cell developmental process. A cDNA complementary to the BCMA cDNA was cloned and sequenced and its presence was assessed by RNase protection assay and anchor-PCR amplification. This antisense-BCMA RNA is transcribed from the same locus as BCMA, and exhibits mRNA characteristic features, e.g. polyadenylation and splicing. It also contains an ORF encoding a putative 115 aa polypeptide, presenting no homology with already known sequences. RNase protection assays demonstrated the simultaneous expression of natural sense and antisense-BCMA transcripts in the majority of human B-cell lines tested.
BCMA is a human gene expressed preferentially in mature B lymphocytes as a 1.2 kb mRNA, which encodes a 184 amino acid peptide (BCMAp). The study of BCMA mRNA expression, using human malignant B cell lines characteristic of different stages of B lymphocyte differentiation, demonstrated that the BCMA mRNA is absent in the pro-B lymphocyte stage. It is expressed faintly at the pre-B cell stage and its expression increases with B lymphocyte maturation. Polyclonal antibodies were used to show, by cellular fractionation and immunoprecipitation, that BCMAp is a non-glycosylated integral membrane protein. Furthermore, BCMAp inserts, in vitro, into canine microsomes, as a type I integral membrane protein. Cell surface labeling showed that BCMAp is not expressed in the plasma membrane of mature B lymphocytes. Immunofluorescence studies revealed that BCMAp lies in a cap-like structure near the nucleus, that was identified as the Golgi apparatus by co-localization of BCMAp with CTR433, a marker of the medial cisternae of the Golgi apparatus. Confocal scanning laser microscopy of U266 plasma cells labeled with markers of various Golgi apparatus subcompartments strongly suggests that BCMAp is located in the cis part of the Golgi apparatus. Thus, BCMAp is the first Golgi resident protein with a tissue specificity and whose expression is linked to the stage of differentiation of B lymphocytes. The location of BCMAp in the Golgi apparatus and its high expression in plasmocytes (secreting large amounts of Ig) suggest that BCMAp is implicated in the intracellular traffic of Ig.
520S troke is a leading cause of death and long-term disabilities worldwide. Despite years of intense research and preclinical identification of numerous potential neuroprotective compounds, the only available treatment for brain ischemia relies on thrombolysis through injection of a recombinant tissuetype plasminogen activator. However, the treatment benefits to <10% of stroke victims because of a narrow therapeutical time window (<4.5 hours after stroke onset) and side effects. Consequently, there is a crucial need for the development of other strategies that could target later phases of the pathophysiological cascade of events after stroke.Since its initial discovery, several studies have highlighted the neuroprotective effect of pituitary adenylate cyclase-activating polypeptide (PACAP) 2 in in vitro and in vivo models of neurodegenerative diseases.3,4 Administered either before or few hours after middle cerebral artery occlusion, PACAP reduces the infarct volume area and improves functional outcomes. [5][6][7] Beside its well-known antiapoptotic activity, the neuropeptide PACAP exerts potent anti-inflammatory properties on innate immune compartment as illustrated by the decrease of the production of proinflammatory mediators interleukin (IL)-12, tumor necrosis factor (TNF)-α, and nitric oxide and the induction of the anti-inflammatory cytokine IL-10 in PACAP-treated macrophages stimulated by lipopolysaccharides.8-10 Whether PACAP acts directly by reducing apoptotic neuronal death 11 or indirectly via modulation of Background and Purpose-Until now, except thrombolysis, the therapeutical strategies targeting the acute phase of cerebral ischemia have been proven ineffective, and no approach is available to attenuate the delayed cell death mechanisms and the resulting functional deficits in the late phase. Then, we investigated whether a targeted and delayed delivery of pituitary adenylate cyclase-activating polypeptide (PACAP), a peptide known to exert neuroprotective activities, may dampen delayed pathophysiological processes improving functional recovery. Methods-Three days after permanent focal ischemia, PACAP-producing stem cells were transplanted intracerebroventricularly in nonimmunosuppressed mice. At 7 and 14 days post ischemia, the effects of this stem cell-based targeted delivery of PACAP on functional recovery, volume lesions, and inflammatory processes were analyzed. Results-The
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