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H Nie

Publications and source records attributed to H Nie.

26 records · Page 2Linked to original sources
PubMed1998

Impact of RNase L overexpression on viral and cellular growth and death.

The biologic actions of interferons (IFNs) are complex and involve multiple biochemical mechanisms, including the 2-5A system, a regulated RNA decay pathway. The 2-5A system is implicated in the antipicornavirus activity of IFN and in the control of apoptosis. To further investigate involvement of the 2-5A system in the control of viral and cellular growth and death, human RNase L cDNA was stably expressed in murine 3T3 cells from a constitutive cytomegalovirus (CMV) promoter. A clonal cell line, 3T3/pLZ, was isolated that overexpressed RNase L by >100-fold compared with levels of the endogenous murine RNase L. Interestingly, human RNase L levels in 3T3/pLZ cells decreased 3-fold as cells entered a confluent, growth arrest state, suggesting autoregulation. Overexpression of human RNase L greatly enhanced both the cell growth inhibitory activity of IFN and the proapoptotic activity of staurosporine. Furthermore, high levels of RNase L suppressed the replication of diverse viruses: encephalomyocarditis virus, vesicular stomatitis virus, human parainfluenza virus-3, and vaccinia virus. Additional reductions in viral growth were obtained by treating 3T3/pLZ cells with IFN (a + beta) before infections. These results directly demonstrate the anticellular and antiviral potential of the 2-5A system.

3T3 Cells↗
PubMed1997

Interferon action and apoptosis are defective in mice devoid of 2',5'-oligoadenylate-dependent RNase L.

2',5'-Oligoadenylate-dependent RNase L functions in the interferon-inducible, RNA decay pathway known as the 2-5A system. To determine the physiological roles of the 2-5A system, mice were generated with a targeted disruption of the RNase L gene. The antiviral effect of interferon alpha was impaired in RNase L-/- mice providing the first evidence that the 2-5A system functions as an antiviral pathway in animals. In addition, remarkably enlarged thymuses in the RNase L-/- mice resulted from a suppression of apoptosis. There was a 2-fold decrease in apoptosis in vivo in the thymuses and spleens of RNase L-/- mice. Furthermore, apoptosis was substantially suppressed in RNase L-/- thymocytes and fibroblasts treated with different apoptotic agents. These results suggest that both interferon action and apoptosis can be controlled at the level of RNA stability by RNase L. Another implication is that the 2-5A system is likely to contribute to the antiviral activity of interferon by inducing apoptosis of infected cells.

Adenine Nucleotides↗
PubMed1997

Effects of intrathecal monoamine antagonists on the nociceptive c-Fos expression in a lesioned rat spinal cord.

Effects of intrathecal (i.t.) administration of monoamine antagonists on formalin-induced neuronal c-Fos expression in two sides of the lumbar dorsal horn were observed in rats with unilateral transection of the dorsolateral funiculus at T11-12 level. The results showed that: 1) pretreated with i.t. normal saline (control) and then an equal volume of formalin was injected into the two hindpaws, the number of Fos-like immunoreactive neurons were 44% lower on the side of lumbar dorsal horn with intact dorsolateral funiculus (57 +/- 3.1 vs. 103 +/- 3.8). 2) Pretreatment with i.t. phentolamine (a non-selective alpha-adrenoceptor antagonist) caused an increase of Fos-like immunoreactive neurons on the intact side so showing only a reduction rate of 23% to the lesioned side (p < .01); 3) pretreatment with i.t. cyproheptadine (a 5-HT-receptor antagonist) caused a similar reduction rate of 21% (p < .01) of Fos-like immunoreactive neurons on the intact side; and 4) combined i.t. pretreatment with phentolamine and cyproheptadine caused a reduction of Fos-like immunoreactive neurons of only 4% on the intact side, namely, the differences in the number of Fos-like immunoreactive neurons on two sides of the lumbar spinal cord owing to the unilateral dorsolateral funiculus lesion were nearly abolished by i.t. coinjection of phentolamine and cyproheptadine. The results indicate that 1) peripheral noxious inputs can provoke a spinally-descending inhibitory effect on the spinal nociceptive transmission via the dorsolateral funiculus and 2) the descending fibers in dorsolateral funiculus exert their action mainly through the release of either norepinephrine or 5-HT at the spinal level.

Adrenergic alpha-Antagonists↗
PubMed1997

Biochemical characterization of the binding of echistatin to integrin alphavbeta3 receptor.

Echistatin is a 49-amino-acid peptide belonging to the family of disintegrins that are derived from snake venoms and are potent inhibitors of platelet aggregation and cell adhesion. Integrin alphavbeta3 receptor plays a critical role in several physiological processes such as tumor-induced angiogenesis, tumor cell metastasis, osteoporosis and wound repair. In this study, we have characterized the binding of echistatin to purified integrin alphavbeta3 receptor and the form expressed on human embryonic kidney 293 cells. We show that both purified and membrane-bound integrin alphavbeta3 binds to echistatin with a high affinity, which can be competed efficiently by linear and cyclic peptides containing the RGD sequence. Previous studies have shown that alphavbeta3 binds to vitronectin in a nondissociable manner, whereas an RGD-containing peptide derived from vitronectin binds in a dissociable manner with a Kd of 9.4 x 10(-7) M. Our studies indicate that radiolabeled echistatin binds to alphavbeta3 in a nondissociable manner, similar to native echistatin. However, echistatin does not support the adhesion of 293 cells expressing alphavbeta3 receptor because of poor binding to plastic dishes and is a potent antagonist of the adhesion of these cells to vitronectin. These studies demonstrate that echistatin binding to alphavbeta3 is of high affinity and irreversible similar to vitronectin and provides an alternate ligand for high-throughput screening for alphavbeta3 antagonists.

Cell Adhesion↗
PubMed1996

A mammalian 2-5A system functions as an antiviral pathway in transgenic plants.

Resistance to virus infections in higher vertebrates is mediated in part through catalysis of RNA decay by the, interferon-regulated 2-5A system. A functional 2-5A system requires two enzymes, a 2-5A synthetase that produces 5'-phosphorylated, 2',5'-linked oligoadenylates (2-5A) in response to double-stranded RNA, and the 2-5A-dependent RNase L. We have coexpressed these human enzymes in transgenic tobacco plants by using a single plasmid containing the cDNAs for both human RNase L and a low molecular weight form of human 2-5A synthetase under control of different, constitutive promoters. Expression of the human cDNAs in the transgenic plants was demonstrated from Northern blots, by specific enzyme assays, and by immunodetection (for RNase L). Infection of leaves, detached or in planta, of the coexpressing transgenic plants by tobacco mosaic virus, alfalfa [correction of alfafa] mosaic virus, or tobacco etch virus resulted in necrotic lesions. In contrast, leaves expressing 2-5A synthetase or RNase L alone and leaves containing the plasmid vector alone produced typical systemic infections. While alfalfa mosaic virus produced lesions only in the inoculated leaves regardless of the concentration of virus in the inoculum, high, but not low, levels of tobacco etch virus inoculum resulted in escape of virus to uninoculated leaves. Nevertheless, there was a substantial reduction of tobacco etch virus yield as measured by ELISA assay in the coexpressing transgenic plants. These results indicate that expression of a mammalian 2-5A system in plants provides resistance to virus infections.

Adenine Nucleotides↗
PubMed1995

Elevated levels of 2',5'-linked oligoadenylate-dependent ribonuclease L occur as an early event in colorectal tumorigenesis.

RNA decay in IFN-treated cells is controlled by 2'5'-linked oligoadenylate (2-5A)-dependent RNase (RNase L), a uniquely regulated endoribonuclease that requires short 5'-phosphorylated, 2-5A for its activity. Because RNase L is also implicated in the regulation of cell proliferation, we monitored its expression in colorectal adenocarcinomas and noncancerous polyps from familial adenomatous polyposis patients. Elevated levels of RNase L mRNA and activity were found in 17 of 20 tumors compared with corresponding normal mucosa. An mAb against RNase L revealed elevated amounts of this RNase in sections of the tumors, largely in the base of the villi. The occurrence of elevated levels of RNase L seems to be an early event in colorectal tumorigenesis, suggesting that control of RNA turnover is an important step in tumor progression. These data also indicate that regulating RNase L activity may be a useful strategy in treating colorectal carcinomas.

Adenocarcinoma↗
PubMed1994

Effect of 24-h blood pressure levels and circadian blood pressure rhythm on left ventricular structure and function in isolated systolic hypertension.

Forty-one participants (mean age 69 +/- 5.6 years) were examined by fully automatic blood pressure monitor and Doppler echocardiography to gain information on the ambulatory blood pressure and the left ventricular structure and function in isolated systolic hypertension. Cumulative sum (cusum)-derived statistics was used to quantify circadian blood pressure rhythm and 24-h blood pressure levels were defined as mean blood pressure values during 24 h, waking (06:00-22:00 h) and sleeping (22:00-06:00 h) periods, respectively. Most of the derivatives of ambulatory blood pressure, including cusum-derived statistics and 24-h blood pressure levels, were significantly related with the left ventricular structural (left ventricular posterior wall and interventricular septum thickness) and functional (acceleration time in the left ventricular outflow tract and early diastolic deceleration time) indexes. Among the left ventricular structural and functional indexes, interventricular septum thickness at end diastole had the strongest correlation with sleeping diastolic mean blood pressure (r = 0.41, P < 0.01), left ventricular posterior wall at end diastole, the best with 24-h systolic mean blood pressure (r = 0.41, P < 0.01), acceleration time the strongest with systolic cusum-derived circadian alteration magnitude (r = 0.49, P < 0.01) and early diastolic deceleration time the greatest with diastolic cusum-derived trough blood pressure (r = 0.45, P < 0.01). We conclude that left ventricular structural changes rely on 24-h systolic and diastolic blood pressure levels, whereas left ventricular functional variations may be more dependent upon circadian blood pressure rhythm in elderly patients with isolated systolic hypertension.

Aged↗