Hydrogen sulfide regulates cAMP homeostasis and renin degranulation in As4.1 and rat renin-rich kidney cells

The present study aims to investigate the regulatory effect of hydrogen sulfide (H(2)S) on cAMP homeostasis and renin degranulation in As4.1 and rat renin-rich kidney cells. It was found in the present study that NaHS at 0.1-10 μM significantly decreased cAMP production in As4.1 cells treated with isoproterenol (a β-adrenoceptor agonist), forskolin (an adenylyl cyclase activator), or 3-isobutyl-1-methylxanthine (IBMX, a phosphodiesterase inhibitor). NaHS at 10 μM suppressed adenylate cyclase activity but stimulated phosphodiesterase activity. We continued to study whether H(2)S may mediate cAMP-dependent renin degranulaion in As4.1 cells. It was found that NaHS at 0.1-10 μM significantly increased intracellular renin protein level. Moreover, NaHS reversed the declined renin content within As4.1 cells and normalized the upregulated renin activity in the culture medium of As4.1 cells treated with the above three stimuli. RT-PCR showed that cystathionine-γ-lyase is the main enzyme to produce endogenous H(2)S in As4.1 cells. Overexpression of cystathionine-γ-lyase increased endogenous H(2)S production and suppressed isoproterenol-induced renin release, suggesting that endogenous H(2)S may also inhibit renin release from As4.1 cells. We also tested whether H(2)S has a similar effect in renin-rich kidney cells. It was found that isoproterenol elevated intracellular cAMP level and extracellular renin activity but decreased renin protein level in the renin-rich kidney cells. Pretreatment with NaHS abolished these effects. In conclusion, H(2)S regulates cAMP homeostasis via inhibition of adenylate cyclase and stimulation of phosphodiesterase. Our findings suggest that H(2)S plays a critical role in regulation of renin degranulation in As4.1 and rat renin-rich kidney cells.     

Distinct role of matrix metalloproteinase-3 in kidney injury molecule-1 shedding by kidney proximal tubular epithelial cells

Tubulointerstitial injury is a common pathway in progressive renal impairment and human proximal tubular epithelial cells (PTEC) play a crucial role in this process. Kidney injury molecule-1 (KIM-1) has received increasing attention due to its potential utility as the therapeutic target and biomarker for kidney injury. This study aims to explore the underlying mechanism regulating the release of KIM-1. Cultured primary human PTEC expressed and released KIM-1 from the apical surface through an ectodomain shedding process mediated by matrix metalloproteinase (MMP), independent of gene expression and protein synthesis. The constitutive KIM-1 shedding by PTEC was enhanced in a dose- and time-dependent manner by human serum albumin (HSA) or tumor necrosis factor-α (TNF-α), two important physiological stimuli found during kidney injury. Data from PCR array screening of MMPs gene expression in PTEC following activation by HSA or TNF-α, and from blocking experiments using either synthetic MMP inhibitors or MMP gene knockdown by siRNA, revealed that the constitutive and accelerated shedding of KIM-1 in cultured PTEC was mediated by MMP-3. Furthermore, the up-regulation of MMP-3 and KIM-1 release by PTEC was associated with generation of reactive oxygen species. In a mouse model of acute kidney injury induced by ischemia and reperfusion, increased expression of MMP-3 and KIM-1 as well as their co-localization were observed in kidney from ischemic but not in sham-operated mice. Taken together, these in vitro and in vivo evidences suggest that MMP-3 plays an inductive role in KIM-1 shedding by PTEC.     

传统环境知识与生物学新课程教学资源

近年来,传统环境知识已成为许多发展中国家在制定和实施国家创新体系和教育发展规划的一种重要知识基础。讨论了传统环境知识的概念,传统知识作为一种课程资源在人才培养以及生物新课程教学中的作用和意义。     

Statins,stem cells,and cancer

The statins (3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors) were proven to be effective antilipid agents against cardiovascular disease. Recent reports demonstrate an anticancer effect induced by the statins through inhibition of cell proliferation, induction of apoptosis, or inhibition of angiogenesis. These effects are due to suppression of the mevalonate pathway leading to depletion of various downstream products that play an essential role in cell cycle progression, cell signaling, and membrane integrity. Recent evidence suggests a shared genomic fingerprint between embryonic stem cells, cancer cells, and cancer stem cells. Activation targets of NANOG, OCT4, SOX2, and c‐MYC are more frequently overexpressed in certain tumors. In the absence of bona fide cancer stem cell lines, human embryonic stem cells, which have similar properties to cancer and cancer stem cells, have been an excellent model throwing light on the anticancer affects of various putative anticancer agents. It was shown that key cellular functions in karyotypically abnormal colorectal and ovarian cancer cells and human embryonic stem cells are inhibited by the statins and this is mediated via a suppression of this stemness pathway. The strategy for treatment of cancers may thus be the targeting of a putative cancer stem cell within the tumor with specific agents such as the statins with or without chemotherapy. The statins may thus play a dual prophylactic role as a lipid‐lowering drug for the prevention of heart disease and as an anticancer agent to prevent certain cancers. This review examines the relationship between the statins, stem cells, and certain cancers. J. Cell. Biochem. 106: 975–983, 2009. © 2009 Wiley‐Liss, Inc.     

甲壳低聚糖铁穴Ⅲ雪、硒配合物的制备及其表征

以甲壳低聚糖与FeCl3反应络合成甲壳低聚糖铁(Ⅲ),以甲壳低聚糖与亚硒酸反应络合成甲壳低聚糖硒,对2种络合物的稳定性及紫外、红外光谱进行检测。甲壳低聚糖铁(Ⅲ)水溶液中不存在游离铁(Ⅲ),表明铁(Ⅲ)与甲壳低聚糖形成了稳定的配合物,在pH值为3～11的范围内不水解,无沉淀产生;甲壳低聚糖硒水溶液中不存在游离的硒离子,表明硒元素与甲壳低聚糖也形成了稳定的配合物。红外光谱扫描也表明甲壳低聚糖与铁、硒络合的特征峰变化。研究结果说明甲壳低聚糖与铁(Ⅲ)或硒能形成稳定的配合物。经红外光谱分析其配位的基团主要是氨基,羟基也有一定的配位能力,但是强度低于氨基。以上实验结果有望使甲壳低聚糖铁(Ⅲ)配合物成为一种具有较好生物利用度的营养型补铁剂,使甲壳低聚糖硒配合物成为具有多功能的保健药品。     

MtnK, methylthioribose kinase, is a starvation-induced protein in Bacillus subtilis

Background  

Methylthioadenosine, the main by-product of spermidine synthesis, is degraded inBacillus subtilisas adenine and methylthioribose. The latter is an excellent sulfur source and the precursor of quorum-sensing signalling molecules. Nothing was known about methylthioribose recycling in this organism.