Disease relevance of Prf1

• Synergistic roles of granzymes A and B in mediating target cell death by rat basophilic leukemia mast cell tumors also expressing cytolysin/perforin [1].
• Cytokine production in the central nervous system of Lewis rats with experimental autoimmune encephalomyelitis: dynamics of mRNA expression for interleukin-10, interleukin-12, cytolysin, tumor necrosis factor alpha and tumor necrosis factor beta [2].
• These results reveal that there may exist a glial cell-dependent cytotoxic pathway within the CNS, and that inducible cytolysin may play an important role in destruction of oligodendrocytes or clearance of infiltrating cells within the CNS in inflammatory diseases such as multiple sclerosis or experimental allergic encephalomyelitis [3].
• Under these conditions a nonlytic cytolysin-RBC intermediate was formed as revealed by hemolysis when cytolysin pretreated cells were washed and resuspended at physiologic ionic strength and pH [4].
• In conclusion, ET-1 secretion in FRTL-5 cells is stimulated via a pertussis toxin-sensitive P1-receptor pathway which is modulated by several signal transduction mechanisms including cAMP, Ca2+, and PKC [5].

High impact information on Prf1

• The noncytotoxic rat mast cell tumor line RBL was transfected with genes for the cytotoxic lymphocyte granule proteins cytolysin (perforin) and granzyme A, giving transfectants with mRNA and protein expression levels comparable with cloned cytotoxic T lymphocytes [6].
• With tumor targets, RBL cells expressing cytolysin alone were weakly cytotoxic, but both cytolytic and nucleolytic activity were enhanced by coexpression of granzyme B [1].
• After permeabilization of mast cells by the bacterial cytolysin streptolysin-O, approximately 60% of the Triton-soluble actin leaks out within 10 min [7].
• The dense core domains contain secretory proteins thought to play a role in cytolysis, including cytolysin and chondroitin sulfate proteoglycan [8].
• The granules of natural killer (NK) cells contain cytolysin and serine proteases, proteins that are expressed specifically in cytolytic cells and are released in response to target binding [9].

Biological context of Prf1

• The amino acid sequence deduced from the nucleotide sequence of the isolated cDNA insert indicates that the mature cytolysin protein consist of 534 amino acids with a leader peptide of 20 amino acids [10].
• IFN-gamma-mediated up-regulation of cytolysin mRNA was markedly more prominent in oligodendrocytes than in microglia and astrocytes [3].
• Cytolysin gene expression in the islets of diabetic BioBreeding/Worcester rats [11].
• Immunocytochemical analyses and Western blots largely confirmed these results: TP2 in steps 9-14, TP1 in steps 12-15, and P1 from late step 11 to step 19 of spermiogenesis [12].
• Immunoelectron microscopy revealed that the epitope is surface exposed, and N-terminal amino acid sequencing of an 8G3-reactive P1 protein from a strain of H. influenzae biogroup aegyptius showed 100% correlation with the published N-terminal amino acid sequence of a P1 protein of H. influenzae type b [13].

Anatomical context of Prf1

• Rat cytolysin is one of the cytolytic factors present in the cytoplasmic granules of rat NK-like cytolytic cells and purified cytolysin exhibits an apparent Mr or 70 kDa [10].
• We have studied the cytotoxic activity of rat basophilic leukemia (RBL) cells transfected with cDNAs for the cytotoxic T lymphocyte (CTL) granule components, cytolysin (perforin), granzyme A, and granzyme B [1].
• Cytolysin mRNA expression in microglia, astrocytes and oligodendrocytes was up-regulated by IFN-gamma [3].
• Induction of cytolysin mRNA in glial cells by IFN-gamma: a possible cytotoxic pathway in the CNS [3].
• These properties of large granular lymphocyte granule cytolysin strongly suggest that it operates through a mechanism similar to the membrane attack of complement [14].

Associations of Prf1 with chemical compounds

• However, the absence of the mannose 6-phosphate modification from cytolysin suggests the existence of yet another targeting system [9].
• Electron microscopy of liposomes exposed to cytolysin in the presence of Ca2+ showed cylindrical structures of 15-nm diameter inserted into the membrane concomitant with the penetration of negative stain into the liposome [14].
• These enzymatic activities are not restricted to only cytolysin-containing granules and are not defined by only the assay of N-alpha-benzyloxycarbonyl-L-lysine thiobenzylesterase activity [15].
• Inhibition by P2 purinergic receptor agonists was comparable to that induced by NAD and ADP-ribose; these compounds were more potent than P1 agonists [16].
• Formation of the cytolysin-RBC intermediate at low ionic strength (250 mM sucrose), pH 7.3, required greater than 0.1 mM calcium [4].

Other interactions of Prf1

• Three stages of cytokine mRNA expression could be distinguished: (i) interleukin (IL)-12, tumor necrosis factor (TNF)-beta (= lymphotoxin-alpha) and cytolysin appeared early and before onset of clinical signs of EAE; (ii) TNF-alpha peaked at height of clinical signs of EAE; (iii) IL-10 appeared increasingly at and after clinical recovery [2].
• On the contrary, LPS strongly inhibited IFN-gamma-mediated cytolysin mRNA expression in microglia, astrocytes and oligodendrocytes [3].

Analytical, diagnostic and therapeutic context of Prf1

• Molecular cloning of rat cytolysin [10].
• We utilized in situ hybridization to detect expression and regulation of cytolysin mRNA in microglia, astrocytes and oligodendrocytes from newborn rat brains [3].
• Kidneys from embryonic 18 (E18)- and 20-day-old (E20) fetuses, postnatal 1 (P1)-, 3 (P3)-, 7 (P7)-, 14 (P14)-, and 21-day-old (P21) pups, and adults were processed for immunohistochemistry and electronmicroscopy [17].
• On Northern-blot analysis with gene-specific oligonucleotide probes, the steady-state mRNA levels of S1, S2, S3, K1 and P1 were all dramatically altered in the SMG of male and female rats treated with propylthiouracil (PTU; 100 mg/litre of drinking water) or thyroxine (T4; 10 micrograms/100 mg body wt.) for 3 weeks [18].
• Potential regulatory DNA elements within the rat protamine P1 promoter region have been identified using gel retardation assays and DNase I footprinting analysis with rat nuclear extracts obtained from different tissues [19].

References