Biomedical subjects

Yi Gu

Publications and source records attributed to Yi Gu.

23 records · Page 2Linked to original sources

PubMed2003

Hematopoietic cell regulation by Rac1 and Rac2 guanosine triphosphatases.

The Rho guanosine triphosphatases (GTPases) Rac1 and Rac2 are critical signaling regulators in mammalian cells. The deletion of both Rac1 and Rac2 murine alleles leads to a massive egress of hematopoietic stem/progenitor cells (HSC/Ps) into the blood from the marrow, whereas Rac1-/- but not Rac2-/- HSC/Ps fail to engraft in the bone marrow of irradiated recipient mice. In contrast, Rac2, but not Rac1, regulates superoxide production and directed migration in neutrophils, and in each cell type, the two GTPases play distinct roles in actin organization, cell survival, and proliferation. Thus, Rac1 and Rac2 regulate unique aspects of hematopoietic development and function.

Actins↗

PubMed2003

The efficiency of humoral immune transfer depends on both the graft and the immunosuppressive treatment.

The present study was designed to compare the efficiency of adoptive transfer of humoral immunity after liver, kidney, and heart transplantation in relation to the number of passenger lymphocytes, and to estimate the risk of a detrimental effect and the chance of a beneficial effect. Hepatitis B virus surface-antigen-vaccinated brown Norway rats (BNs) and AxC 9935 Irish (ACI rats) served as donors, and naïve Lewis (LEW) rats as recipients. The liver grafts contained 100 times more passenger lymphocytes than heart grafts, and the kidney grafts approximately ten times more, indicated by monoclonal CD45 antibody staining. Transient anti-HBs immunity did occur after transplantation of all three organ grafts. In all rejecting groups, the serum recipient-to-donor anti-HBs titer ratio (R/D ratio) was below 0.10%, with heart recipients showing half the level (0.05%) of liver recipients (0.09%). Under immunosuppression, R/D ratio doubled in liver or kidney recipients, but remained unaffected in heart recipients. Immune transfer was most efficient in immune-suppressed liver recipients in the spontaneously tolerant strain combination as indicated by a significantly higher R/D ratio (0.32%) and a longer titer persistence (up to 9 weeks) than in all other groups. Therefore, mainly liver and kidney graft recipients carry a risk, but also a chance of benefiting from the transfer of donor-derived immunity.

Animals↗

PubMed2003

[Inhibitory action of berberine on glucose absorption].

AIM: To study the absorption characteristics of berberine and its influence on glucose absorption. METHODS: Rat recirculating perfusion model was used to study berberine absorption characteristics and Caco-2 cell model was used to explore the influence of berberine on disaccharidase, using HPLC to assay the appearance of glucose to indicate enzyme activities. RESULTS: Berberine was found to be hardly absorbed in the intestine (less than 5% in 2.5 h). However, sucrase and maltase activities were found to be inhibited by berberine, its ID50 to sucrase is 1.830 mg.L-1, and showed no dose dependent influence on maltase activity. Berberine also showed influence on glucose absorption. However, this effect is not significant. CONCLUSION: Berberine may act as an alpha-glucosidase inhibitor, which is its main mechanism in diabetes treatment.

Animals↗

PubMed2002

RAC2 GTPase deficiency and myeloid cell dysfunction in human and mouse.

Rho GTPases including Rho, Rac, and Cdc42 act as intracellular molecular switches to control cellular responses such as actin cytoskeleton rearrangement, gene transcription, cell growth, and possibly transformation. Their roles have been increasingly implicated in activation of signaling processes in leukocytes including integrin-mediated signal transduction and growth factor-induced cell survival and proliferation pathways. In particular, functional disruption of Rac2, a hematopoietic-specific Rho GTPase, causes severe myeloid cell dysfunction in both mouse and man. Rac2-deficient mice and a human patient with a D57N Rac2 mutant share a phenotype of leukocytosis with defective neutrophil chemotaxis and superoxide production in response to some, but not all, agonists. Our studies also suggested that the phenotypic abnormalities associated with D57N may involve not only neutrophil cellular functions, but also abnormal cell survival in other hematopoietic cells. Together, these data demonstrate a critical and unique role for Rac2 in normal neutrophil function and define a new genetic immunodeficiency syndrome in humans.

Animals↗

PubMed2002

Rac2, a hematopoiesis-specific Rho GTPase, specifically regulates mast cell protease gene expression in bone marrow-derived mast cells.

Rho family GTPases activate intracellular kinase cascades to modulate transcription of multiple genes. Previous studies have examined the roles of the ubiquitously expressed Rho GTPase, Rac1, in regulation of gene expression in cell lines and implicated NF-kappaB, serum response factor, and kinase signaling pathways in this regulation. To understand the role of the closely related but hematopoiesis-specific Rho GTPase, Rac2, in regulation of gene transcription, we compared the gene expression profiles between wild-type and Rac2(-/-) bone marrow-derived mast cells. Our data demonstrate remarkable specificity in the regulation of gene expression by Rac2 versus Rac1. Microarray analysis demonstrated that expression of 38 known genes was significantly altered in Rac2(-/-) mast cells after cytokine stimulation compared with those in wild-type cells. Of these, the expression of the mouse mast cell protease 7 (MMCP-7) gene in wild-type cells was highly induced at the transcriptional level after stimulation with stem cell factor (SCF). In spite of compensatorily increased expression of Rac1 in Rac2-deficient cells, SCF-induced MMCP-7 transcription did not occur. Surprisingly, the loss of MMCP-7 induction was not due to decreased activation of NF-kappaB, a transcription factor postulated to lie downstream of Rac1 and known to play a critical role in hematopoietic cell differentiation and proliferation. However, the activities of c-Jun N-terminal kinases (JNKs) were markedly decreased in Rac2(-/-) mast cells. Our results suggest that cytokine-stimulated activation of MMCP-7 gene transcription is selectively regulated by a Rac2-dependent JNK signaling pathway in primary mast cells and imply a remarkable specificity in the regulation of transcriptional activity by these two highly related Rho GTPases.

Amino Acid Motifs↗