Biomedical subjects

Zheng Xing

Publications and source records attributed to Zheng Xing.

4 recordsLinked to original sources

PubMed2004

Possible induction of diabetes by treatment of hypertension with indapamide (with four case reports).

OBJECTIVE: To study therapy with indapamide impairing carbohydrate metabolism in essential hypertension patients and achieve earlier prevention, diagnoses and treatment of diabetes induced by indapamide. METHODS: Four cases of essential hypertension patients (1 male and 3 females) were observed through process of therapy with indapamide and laboratory investigations. RESULTS: After 4- to 14-month period of therapy with the combination of indapamide (2.5 mg/day) and fosinopril (10 mg/day) in three patients and 6-month period of monotherapy with indapamide (2.5 mg/day) in one patient, glucose levels of all patients increased and achieve criteria of diabetes diagnoses. After 3- to 13-month period of therapy without indapamide, glucose levels of all patients decreased and diabetes disappeared. CONCLUSION: Therapy with indapamide may induce diabetes in essential hypertension patients. After stopping indapamide, glucose tolerance impairing may be reversed.

Adult↗

PubMed2003

Essential role of survivin, an inhibitor of apoptosis protein, in T cell development, maturation, and homeostasis.

Survivin is an inhibitor of apoptosis protein that also functions during mitosis. It is expressed in all common tumors and tissues with proliferating cells, including thymus. To examine its role in apoptosis and proliferation, we generated two T cell-specific survivin-deficient mouse lines with deletion occurring at different developmental stages. Analysis of early deleting survivin mice showed arrest at the pre-T cell receptor proliferating checkpoint. Loss of survivin at a later stage resulted in normal thymic development, but peripheral T cells were immature and significantly reduced in number. In contrast to in vitro studies, loss of survivin does not lead to increased apoptosis. However, newborn thymocyte homeostatic and mitogen-induced proliferation of survivin-deficient T cells were greatly impaired. These data suggest that survivin is not essential for T cell apoptosis but is crucial for T cell maturation and proliferation, and survivin-mediated homeostatic expansion is an important physiological process of T cell development.

Animals↗

PubMed2003

Interdimer processing mechanism of procaspase-8 activation.

The execution of apoptosis depends on the hierarchical activation of caspases. The initiator procaspases become autoproteolytically activated through a less understood process that is triggered by oligomerization. Procaspase-8, an initiator caspase recruited to death receptors, is activated through two cleavage events that proceed in a defined order to generate the large and small subunits of the mature protease. Here we show that dimerization of procaspase-8 produces enzymatically competent precursors through the stable homophilic interaction of the procaspase-8 protease domain. These dimers are also more susceptible to processing than individual procaspase-8 molecules, which leads to their cross-cleavage. The order of the two interdimer cleavage events is maintained by a sequential accessibility mechanism: the separation of the large and small subunits renders the region between the large subunit and prodomain susceptible to further cleavage. In addition, the activation process involves an alteration in the enzymatic properties of caspase-8; while procaspase-8 molecules specifically process one another, mature caspases only cleave effector caspases. These results reveal the key steps leading to the activation of procaspase-8 by oligomerization.

Apoptosis↗

PubMed2002

c-FLIP(L) is a dual function regulator for caspase-8 activation and CD95-mediated apoptosis.

Activation of the caspase cascade is a pivotal step in apoptosis and can occur via death adaptor-mediated homo-oligomerization of initiator procaspases. Here we show that c-FLIP(L), a protease-deficient caspase homolog widely regarded as an apoptosis inhibitor, is enriched in the CD95 death-inducing signaling complex (DISC) and potently promotes procaspase-8 activation through hetero-dimerization. c-FLIP(L) exerts its effect through its protease-like domain, which associates efficiently with the procaspase-8 protease domain and induces the enzymatic activity of the zymogen. Ectopic expression of c-FLIP(L) at physiologically relevant levels enhances procaspase-8 processing in the CD95 DISC and promotes apoptosis, while a decrease of c-FLIP(L) expression results in inhibition of apoptosis. c-FLIP(L) acts as an apoptosis inhibitor only at high ectopic expression levels. Thus, c-FLIP(L) defines a novel type of caspase regulator, distinct from the death adaptors, that can either promote or inhibit apoptosis.

Apoptosis↗