J z du’s scientific contributions zhejiang university, hangzhou (zju) and other places brain anoxia

[show abstract] [hide abstract] ABSTRACT: prolactin (PRL) is a multifunctional hormone that influences multiple physiological processes. It has been shown to have a protective effect on the cardiovascular system; however, the mechanisms of this effect are poorly understood. The purpose of the study was to elucidate the role of PRL in intermittent hypoxia (IH)-induced apoptosis in the cardiovascular system.

We established a hyperprolactinemic rat model by implanting two anterior pituitary (AP) glands into the renal capsule of male sprague-dawley rats. The rats were kept under normoxic conditions for 4weeks after implantation in order to reach the expression plateau of PRL in the plasma, and then treated with IH for 7 or 14days.Brain anoxia


their hearts were then removed for histological and protein expression analyses. Cerebral cortex (CX)-grafted control rats challenged with IH displayed unique phenotypes such as a thicker heart wall, an abnormal myocardial architecture and an increased interstitial space of the left ventricle. They exhibited reduced expressions of p-JAK2, p-STAT5, cell cycle-dependent proteins (cyclin D1, cyclin E and cyclin A), IGF-irα, pi3kα, p-AKT and p-ERK1/2 in cardiomyocytes at 7days.

Our comprehensive analysis suggested that high plasma PRL can protect rat cardiomyocytes against IH through (1) the p-JAK2 and p-STAT5 pathways for transient cell proliferation, (2) the pi3kα/AKT and MAPK survival pathways through IGF-I, and (3) the downregulation of IGF-II and ERK5, which inhibit cell hypertrophy.Brain anoxia

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[show abstract] [hide abstract] ABSTRACT: neurons in the mammalian central nervous system are extremely vulnerable to oxygen deprivation and blood supply insufficiency. Indeed, hypoxic/ischemic stress triggers multiple pathophysiological changes in the brain, forming the basis of hypoxic/ischemic encephalopathy. One of the initial and crucial events induced by hypoxia/ischemia is the disruption of ionic homeostasis characterized by enhanced K(+) efflux and na(+)-, ca(2+)- and cl(-)-influx, which causes neuronal injury or even death. Recent data from our laboratory and those of others have shown that activation of opioid receptors, particularly delta-opioid receptors (DOR), is neuroprotective against hypoxic/ischemic insult.Brain anoxia this protective mechanism may be one of the key factors that determine neuronal survival under hypoxic/ischemic condition. An important aspect of the DOR-mediated neuroprotection is its action against hypoxic/ischemic disruption of ionic homeostasis. Specially, DOR signal inhibits na(+) influx through the membrane and reduces the increase in intracellular ca(2+), thus decreasing the excessive leakage of intracellular K(+). Such protection is dependent on a PKC-dependent and PKA-independent signaling pathway. Furthermore, our novel exploration shows that DOR attenuates hypoxic/ischemic disruption of ionic homeostasis through the inhibitory regulation of na(+) channels. In this review, we will first update current information regarding the process and features of hypoxic/ischemic disruption of ionic homeostasis and then discuss the opioid-mediated regulation of ionic homeostasis, especially in hypoxic/ischemic condition, and the underlying mechanisms.Brain anoxia

[show abstract] [hide abstract] ABSTRACT: diminished oxygen concentration within growing tumors may stimulate neovascularization by inducing both up-regulation of angiogenic factors and down-regulation of antiangiogenic agents. A potentially important molecule in the growth of pituitary adenomas is prolactin (PRL), which can be cleaved by cathepsin-D to yield a 16-kda form (16K-PRL) with potent antiangiogenic effects. We examined the expression of PRL in cultured GH4C1 pituitary adenoma cells after exposure to hypoxia (0.1% oxygen) for periods of 12 to 36 hours. In contrast to increased expression of the angiogenic factor vascular endothelial growth factor in hypoxic cells, PRL mrna and levels of intracellular and secreted PRL were significantly reduced under hypoxia.Brain anoxia the reduction was not attributable to a general suppression of either transcription or protein synthesis. Although 16K-PRL was not evident in conditioned medium at physiologic ph, lowering the ph to mimic the acidic tumor microenvironment resulted in generation of 16K-PRL, which was sharply reduced in medium drawn from hypoxic cells. Production of 16K-PRL was blocked by the cathepsin-D inhibitor pepstatin-A, and the reduced 16K-PRL formation in hypoxic-conditioned medium correlated with a decrease in secretion of cathepsin-D and its precursor, procathepsin-D. Thus, hypoxia acts upon GH4C1 cells to increase vascular endothelial growth factor expression, decrease PRL synthesis, and suppress conversion of PRL to 16K-PRL via inhibition of cathepsin-D proteolysis.Brain anoxia these mechanisms may act in concert to stimulate angiogenesis in prolactinomas.

[show abstract] [hide abstract] ABSTRACT: cells in the preoptic area (POA), arcuate nucleus (ARC) and ventromedial nucleus (VMN) that possess estrogen receptor alpha (eralpha) mediate estradiol feedback to regulate endocrine and behavioral events during the estrous cycle. A percentage of eralpha cells located in the ARC and VMN express somatostatin (SST) and are activated in response to estradiol. The aims of the present study were to a) investigate the location of c-fos, a marker for activation, in cells containing eralpha or SST at various times during the follicular phase, and b) determine if lipopolysaccharide (LPS) administration, which leads to disruption of the LH surge, is accompanied by altered eralpha and/or SST activation patterns.Brain anoxia follicular phases were synchronized with progesterone vaginal pessaries and control animals were killed at 0, 16, 31 or 40 h (n = 4-6/group) after progesterone withdrawal (PW; time zero). At 28 h, other animals received LPS (100 ng/kg) and were subsequently killed at 31 h or 40 h (n = 5/group). Hypothalamic sections were immunostained for c-fos and eralpha or SST. LH surges occurred only in control ewes with onset at 36.7 ± 1.3 h after PW: these animals had a marked increase in the percentage of eralpha cells that co-localized c-fos (%eralpha/c-fos) in the ARC and mpoa from 31 h after PW and throughout the LH surge. In the VMN, %eralpha/c-fos was higher in animals that expressed sexual behavior compared to those that did not.Brain anoxia SST cell activation in the ARC and VMN was greater during the LH surge compared to other stages in the follicular phase. At 31 or 40 h after PW (i.E., 3 or 12 h after treatment, respectively), LPS decreased %eralpha/c-fos in the ARC and the mpoa but there was no change in the VMN compared to controls. The %SST/c-fos increased in the VMN at 31 h after PW (i.E., 3 h after LPS) with no change in the ARC compared to controls. These results indicate that there is a distinct temporal pattern of eralpha cell activation in the hypothalamus during the follicular phase, which begins in the ARC and mpoa at least 6-7 h before the LH surge onset, and extends to the VMN after the onset of sexual behavior and the LH surge.Brain anoxia furthermore, during the surge, some of these eralpha activated cells may be SST secreting cells. This pattern is markedly altered by acute LPS administered during the late follicular phase indicating that the disruptive effects of this stressor are mediated by suppressing eralpha cell activation at the level of the mpoa and ARC, and enhancing SST-cell activation in the VMN, leading to the attenuation of the LH surge.