1.Some recent advances in the molecular mechanisms underlying senescence
Chinese Journal of Pathophysiology 1986;0(01):-
Aging or senescence is a process in which individuals undergo an exponential decline in vitality, leading to death. Recent years,much progress on the molecular mechanisms underlying senescence have been made. (1) Some senescence-related gene such as SEN6A,hic-5,din1 and MORF 4 have been clarified; (2) In 1997, through a set of experiments sponsered by scientists of Department of Biology Massachusetts Institute of Technology, it was found that the accommulation of extrachromosomal rDNA circles (ERC) in budding yeasts nucleolus is responsible for cell-senescence and the researchers propose that when enough of these circles accumulate, they clog the nucleus and prevent the cell from reading or replicating its genome, causing it to stop dividing and ultimately to die; (3) In another work finished by National Institute on Aging and the Geron biotech company of Melo, it was proved that a cells biological clock,which tells the cell how and how many times to divide, lies in its telomeres, little bits of DNA that coat the tips of the chromosome and it was clarified that a powerful enzyme,telomerase, with the potential to rejuvenate the human bodys aging tissues could effectively extend the shortened telomere . Although there is a long way to go, scientists still believe that it will be made reality in the future to greatly extend the life-span of human.
2.Recent advances in urotensin-Ⅱ research
Chinese Journal of Pathophysiology 2000;0(08):-
Urotensin-Ⅱ is a vasoactive 'somatestatin-like' cyclic peptide. Recently, human urotensin-Ⅱ has been cloned and demonstrated to be the most potent vasoconstrictor identified so far. The receptor of urotensin-Ⅱ has now been identified as the orphan receptor GPR 14 . This peptide may influence cardiovarscular homeostasis, pathology and also influence respiratory system, central nervous system and endocrine function.
3.Pressure-related activation of inducible nitric oxide synthase
Dunyong TAN ; Xu PENG ; Chaoshu TANG
Chinese Journal of Pathophysiology 2001;17(8):792-
A lot of reports suggested that inducible nitric oxide synthase (iNOS) has a very different nature from constitutive NOS including endothelial NOS (eNOS) and neural NOS (nNOS). When exposed to cytokines or bacterial products, iNOS could be greatly activated and produces hundreds or thousands fold more NO than it does usually. Whether iNOS activation is arterial pressure related is not clear. In the present experiment, we studied three groups(n=6) of Sprague Dawley (SD) rats with implanted aorta and venous catheters that were maintained on 1 mEq/d, 12.5 mEq/d and 25 mEq/d of sodium intake respectively. Pulsatile arterial pressure signals from the amplifier were sent to a digital computer and the urine samples were taken every other day for nitrate/nitrite excretion (UNOx) assay using Greiss Reaction. After 6 days infusion, the rats were euthanized with an overdose of sodium pentobarbital, and the renal medullas were rapidly removed and frozen on dry ice for iNOS activity assay. Morever separate groups of hypertensive rats including spontaneously hypertensive rat (SHR, n=6) and High NaCl-induced hypertensive rat (NaHR, n=6) were used to measure renal iNOS protein by Western Blotting. The results showed that the mean arterial pressure (MAP) were significantly increased with the increase intake of sodium, the MAP (mmHg) at day 6 were 99.6±3.5,116.65±4.2 and 125.43±4.5, and the iNOS activity (nmol*g-1 protein*min-1) were 122.3±23.4, 342.4±35.6 and 623.9±65.4 in 1 mEq/d, 12.5 mEq/d and 25 mEq/d of sodium intake-rats respectively. At the same time, UNOx at day 6 were also increased, in turn, to 5 865.6±343.0 (for 12.5 mEq/d intake-rats) and (9 642.8±1 045.3) (for 25 mEq/d sodium intake-rats) nmol/d from (3 834.9±234.8) nmol/d of 1 mEq/d sodium intake-rats respectively. Western blotting showed that the renal medullary iNOS protein in SHR and NaHR were increased by 178%±13% and 104%±9% of normal Wistar rats. The data indicates that elevated arterial pressure could be an effective stimulus for iNOS activation.
4.Influence of transcription factor Stat5a on proliferation of human breast cancer cells and its epigenetic mechanisms
Jie ZHANG ; Peizhi TANG ; Jianjun HUANG ; Dunyong TAN
Chongqing Medicine 2015;(19):2596-2599
Objective To investigate and clarify the effect of Stat5a on proliferation of human breast cancer cells (MCF‐7) and to detect the changes of epigenetic signature on the promoter region of p53 gene .Methods Stat5a was over expressed in human breast cancer cells (MCF‐7) by using adenovirus mediated gene transfer technology .The cell proliferation was examined by MTS assay .ChIP assay was used to check the trimethylation of lysine 27 on histone 3 (H3K27Me3) of p53 gene promoter region .Fur‐thermore ,qRT‐PCR and western blot were also applied to confirm the expression of p53 gene .Results The number of MCF 7 in‐creased in a dose dependent manner .Compared with that of control group ,the cell density of MCF‐7 increased 7 .603 1% , 18 .123 7% and 24 .898 7% when the MOI were 10 ,20 and 30 .Chromatin Immunoprecipitation showed that Stat5a significantly in‐creased H3K27Me3 and down regulated the expression level of p53 gene .Conclusion Stat5a promotes proliferation of breast cancer cells through trimethylation of H3K27 and inhibition of p53 gene expression .
5.Progress in mitochondrial nitric oxide synthase
Xiaosi SUN ; Dunyong TAN ; Huadong WANG ; Liang YAN
Chinese Journal of Pathophysiology 2000;0(12):-
Nitric oxide (NO) is an intra- and intercellular messenger with a broad spectrum of activities in the central nervous system, cardiovascular and immune systems. Mitochondrial nitric oxide synthase(mtNOS), which might be a new form of NOS in mitochondria, has been discovered to be active in the regulation of mitochondrial respiration, energy metabolism and many pathophysiological processes. In this review, the location, properties, physiological and pathophysiological significance of mtNOS were summarized.
6.Inducible nitric oxide synthase and arterial pressure regulation
Shaobing CHENG ; Dunyong TAN ; Xiaolin CHEN ; Haozhuang YANG ; Suimei ZHANG ; Liang YAN
Chinese Journal of Pathophysiology 1989;0(05):-
AIM and MEfTHODS: To clarify the role of inducible nitric oxide synthase (iNOS) in the regula- tion of blood pressure, in the present study, we examined the effect of aminoguanidine (AG), a selective inhibitor of iNOS on the hemodinamical response of Dahl salt - sensitive (DS) and Dahl salt - resistant (DR) rats to low (0. 3% ) or high (8%) sodium chloride (Nacl) infusion by chronical in vivo hemodynamic experiment, and the effect of NaCl or NaCl plus AG infusion on urinary nitrate (NO3)/nitrite (NO2), the end product of nitric oxide (NO),ex- cretion by Greiss Reaction. Furthermore, NOS activity assay was the dried out to probe the effect of NaCl and AG on calcium - dependent or independent NOS activity in renal tissue. RESULTS:1. High or low NaCl - infused DR rats and low NaCl - infused DS rats have no hemodinamical response to AG, however, the hpertensive effect of high NaCl (8% ) infusion on DS rats were gnatly amplified by co - infusion of AG. 2. Administration of high NaCl signif- icantly elevated the iNOS activity of renal tissue, and greatly increased urinary NO3/NO2 excretion. CONCLUSION: Ihducthle NOS is an important modulator of arterial pressure, especially in case of higher blood pressure.
7.Effect of mycobacterium bovis bacillus calmette-guerin vaccination on arterial pressure in hypertensive rats
Dunyong TAN ; Xiaolin CHEN ; Shaobing CHENG ; Chao ZHANG ; Jun DONG ; Liang YAN
Chinese Journal of Pathophysiology 2001;17(6):501-505
AIM: The present study was designed to examine the effect of Bacillus Calmette-Guerin (BCG) vaccination on blood pressure, nitric oxide (NO) production and iNOS expression in hypertensive rats. METHODS: Renal hypertension (RH) were made by renal artery stenosis in SD rats and the sodium induced hypertensive (SH) rats were made by feeding the rats with high sodium chloride diet (5 g NaCl/100 g food). After four weeks, the hypertensive animals were subjected to the experiment. All the rats were vaccinated with BCG (0.1 mL, i.d) and blood pressure were examined every week. Greiss reaction was used to measure the urinary NO excretion and Western blot was applied to probe the iNOS protein expression in aortic tissue. RESULTS: It was shown that one week after BCG vaccination, the blood pressure decreased significantly in hypertensive rats induced by NaCl-overloading and renal artery stenosis, but not in normotensive control rats. Furthermore, the hypotensive effect of BCG vaccination was enhanced by co-administration of L-arginine. A significant increase in NO production was observed in hypertensive rats. Also, Western blot showed BCG vaccination led to an obvious increase in iNOS expression in the aortic tissue of hypertensive, but not of normal control rats. CONCLUSION: BCG vaccination could lower the blood pressure of hypertensive rats through activation of iNOS/NO pathway.
8.Electrical stimulation of POAH alters firing rates of IL-1β-treated thermosensitive neurons in the VSA in rabbits
Jun DONG ; Daxiang LU ; Yongmei FU ; Liang YAN ; Dunyong TAN ; Chujie LI
Chinese Journal of Pathophysiology 2000;16(9):783-787
AIM and METHODS: To investigate the functional connection between the preoptic anterior hypothalamus (POAH) and the ventral septal area (VSA) in fever mechanism, the firing rates of thermosensitive neurons in the VSA of 26 New Zealand white rabbits were recorded using extracellular microelectrode technique. RESULTS: The firing rates in both types of thermosensitive neurons in the VSA had no significant changes after intracerebroventricular (icv) injection of artificial cerebrospinal fluid(ACSF). When interleukin-1β (IL-1β) was given (icv), the firing rate of the warm-sensitive neurons was increased significantly and that of the cold-sensitive neurons was decreased remarkably. The effects of IL-1β on the changes of firing rate in thermosensitive neurons of the VSA were reversed by electrical stimulation of the POAH. CONCLUSION: The roles of positive and negative thermoregulatory centers in the interaction between the POAH and VSA are closely linked during endogenous pyrogen induced fever.
9.Effect of mycobacterium bovis bacillus calmette-guerin vaccination on arterial pressure in hypertensive rats
Dunyong TAN ; Xiaolin CHEN ; Shaobing CHENG ; Chao ZHANG ; Jun DONG ; Liang YAN
Chinese Journal of Pathophysiology 1989;0(06):-
AIM: The present study was designed to examine the effect of Bacillus Calmette-Guerin (BCG) vaccination on blood pressure, nitric oxide (NO) production and iNOS expression in hypertensive rats. METHODS: Renal hypertension (RH) were made by renal artery stenosis in SD rats and the sodium induced hypertensive (SH) rats were made by feeding the rats with high sodium chloride diet (5 g NaCl/100 g food). After four weeks, the hypertensive animals were subjected to the experiment. All the rats were vaccinated with BCG (0 1 mL, i.d) and blood pressure were examined every week. Greiss reaction was used to measure the urinary NO excretion and Western blot was applied to probe the iNOS protein expression in aortic tissue. RESULTS: It was shown that one week after BCG vaccination, the blood pressure decreased significantly in hypertensive rats induced by NaCl-overloading and renal artery stenosis, but not in normotensive control rats. Furthermore, the hypotensive effect of BCG vaccination was enhanced by co-administration of L-arginine. A significant increase in NO production was observed in hypertensive rats. Also, Western blot showed BCG vaccination led to an obvious increase in iNOS expression in the aortic tissue of hypertensive, but not of normal control rats. CONCLUSION: BCG vaccination could lower the blood pressure of hypertensive rats through activation of iNOS/NO pathway. [
10.Effects of electrical stimulation of VSA on the firing of thermosensitive neurons in the POAH of rabbits
Jun DONG ; Daxiang LU ; Yongmei FU ; Liang YAN ; Renbin QI ; Dunyong TAN ; Suimei ZHANG ; Shaobing CHENG ; Haozhuang YANG ; Chujie LI
Chinese Journal of Pathophysiology 2001;17(5):411-414
AIM and METHODS:To investigate the effect of electrical stimulation of VSA on the firing of thermosensitive neurons in preoptic anterior hypothalamus (POAH), the firing rate of thermosensitive neurons in POAH of 20 New Zealand white rabbits was recorded by using extracellular microelectrode techinque. RESULTS:(1)Electrical stimulation of ventral septal area (VSA) caused a significant increase in firing rate of warm-sensitive neurons in the preoptic area of the anterior hypothalamus(POAH).(2) The firing rate of cold-sensitive neurons was decreased remarkably in the POAH by electrical stimulation of VSA. CONCLUSION:VSA may play a controlling role in the thermoregulation through altering the firing rate of thermosensitive neurons in the POAH.