细胞凋亡与疾病

细胞凋亡(apoptos is)是普遍存在于人体组织细胞内的细胞死亡的形式之一,是不同于坏死的正常生理性的程序性细胞死亡。细胞抗凋亡是生物机体为了适应环境变化,维持生理平衡的一种主动的自我保护行为。凋亡或抗凋亡均是在基因控制下,多样性、偶联性、多途径的信号转导过程。它也受到内外生存因子的影响和制约,肿瘤等多种疾病均能影响细胞凋亡过程。     

Caspase非依赖性细胞死亡的研究进展

细胞凋亡是一种生理性细胞死亡机制，它是由多基因调控的一种细胞的主动的自杀性过程。一般认为它是由蛋白酶caspases通过两种途径激活的。但是，近年来研究发现除caspases引起的细胞凋亡外，还有caspases非依赖性的细胞死亡形式存在，包括细胞的自我吞噬作用、细胞蛋白酶体的降解和线粒体途径。这些途径无论是在试验的条件下还是在生理或病理的情况下都可以观察到。目前认为凋亡诱导因子(AIF)在caspases非依赖性的细胞死亡中起关键作用。     

三肽囊素对环磷酰胺诱导的免疫器官细胞凋亡的影响

研究了三肽囊素对环磷酰胺诱导的鸡免疫抑制模型中免疫器官细胞凋亡的影响。将180只1日龄粤黄鸡随机分成环磷酰胺组、正常对照组、三肽囊素组以及三肽囊素 环磷酰胺组。利用末端脱氧核苷酸转移酶介导的dTUP缺口末端标记法(TUNEL)，对不同组鸡的免疫器官细胞凋亡进行计数。结果发现，环磷酰胺组细胞凋亡数比对照组明显增多(P＜0．05)，而三肽囊素 环磷酰胺组细胞凋亡数显著少于环磷酰胺组(P＜O．05)；三肽囊素组的细胞凋亡数比环磷酰胺组少，且差异显著(P＜0．05)。由此可知，三肽囊素对环磷酰胺所诱导的细胞凋亡具有抑制作用。     

Melatonin reduces apoptotic cells,SOD2 and HSPB1 and improves the in vitro production and quality of bovine blastocysts

Effects of adding different concentrations of melatonin (10^?7, 10^?9 and 10^?11 M) to maturation (Experiment 1; Control, IVM  + 10^?7, IVM  + 10^?9, IVM  + 10^?11) and culture media (Experiment 2; Control, IVC  + 10^?7, IVC  + 10^?9, IVC  + 10^?11) were evaluated on in vitro bovine embryonic development. The optimal concentration of melatonin (10^?9 M) from Experiments 1–2 was tested in both maturation and/or culture media of Experiment 3 (Control, IVM  + 10^?9, IVC  + 10^?9, IVM /IVC  + 10^?9). In Experiment 1, maturated oocytes from Control and IVM  + 10^?9 treatments showed increased glutathione content, mitochondrial membrane potential and percentage of Grade I blastocysts (40.6% and 43%, respectively). In Experiment 2, an increase in the percentage of Grade I blastocysts was detected in IVC  + 10^?7 (43.5%; 56.7%) and IVC  + 10^?9 (47.4%; 57.4%). Moreover, a lower number and percentage of apoptotic cells in blastocysts were observed in the IVC  + 10^?9 group compared to Control (3.8 ± 0.6; 3.6% versus 6.1 ± 0.6; 5.3%). In Experiment 3, the IVC  + 10^?9 treatment increased percentage of Grade I blastocysts with a lower number of apoptotic cells compared to IVM /IVC  + 10^?9 group (52.6%; 3.0 ± 0.5 versus 46.0%; 5.4 ± 1.0). The IVC  + 10^?9 treatment also had a higher mRNA expression of antioxidant gene (SOD 2) compared to the Control, as well as the heat shock protein (HSPB 1) compared to the IVM  + 10^?9. Reactive oxygen species production was greater in the IVM /IVC  + 10^?9 treatment group. In conclusion, the 10^?9 M concentration of melatonin and the in vitro production phase in which it is used directly affected embryonic development and quality.     

Phenolic extract of Morchella angusticeps peck inhibited the proliferation of HepG2 cells in vitro by inducing the signal transduction pathway of p38/MAPK

Morchella angusticeps Peck, one of the most popular edible mushrooms, has attracted great attention due to its delicious taste and healthy properties. However, both its biological effects and the possible mechanism of action have not yet been known. We investigated the anti-proliferative activity of the phenolic extract derived from Morchella angusticeps Peck (MPE) against HepG2 human hepatocellular carcinoma cells. Results showed that MPE at non-cytotoxicity doses significantly inhibited the proliferation of HepG2 cells in a dose-dependent manner with inhibitory rates ranging from 18 to 90% (P<0.01). The possible mechanism might be that MPE induced apoptosis through initiating the mitochondrial death pathway by regulating Bax, Bcl-2 and cleaved caspase-3. On the other hand, MPE might trigger cell cycle arrest at G₀/G₁/S phases by managing p21, Cyclin D1, cyclin-dependent kinases-4 (CDK4) and proliferating cell nuclear antigen (PCNA). Additionally, MPE downregulated TRAF-2 and p-p53, while upregulated p-ASK1 and p-p38. Therefore, it could be inferred that MPE might induce the anti-proliferative function to HepG2 cells through the p38/MAPK signal transduction pathway.     

铅和（或）镉对体外培养肾细胞的毒性损伤

在培养液中加入不同浓度的Cd（10、20、40μmol／L）、Pb（10、20、40μmol／L）和Pb-Cd联合（分别为5、10、20μmol／L），来探讨铅镉对肾细胞的作用及可能机制。在显微镜下观察细胞形态、测定细胞凋亡率和细胞周期及上清液脂质过氧化指标。结果表明：20μmol／L以上染毒组细胞皱缩、体积变小，表面有细胞碎片，甚至呈泡沫状或树枝状；铅、镉单独和联合染毒组GSH—Px、SOD活性随染毒剂量的增加，呈逐渐下降趋势（P〈0．05）．而MDA含量和凋亡率则呈升高趋势（P〈0．05），并存在剂量和时间效应。镉和铅也能使细胞周期停滞。Pb、Cd联合可加剧细胞损伤。     

Liraglutide ameliorates liver injury of type 2 diabetic mice via micro-RNA-33-AMPK pathway

AIM: To observe the effects of liraglutide on the level of microRNA-33 (miR-33) and the expression of AMP-activated protein kinase (AMPK) and apoptosis-related proteins in mice with type 2 diabetes mellitus (T2DM), and to explore its possible mechanism. METHODS: High-fat diet and intraperitoneal injection of streptozocin were used to establish the type 2 diabetic model in C57BL/6 mice. The mice were randomly divided into 4 groups (n=15):in control group, the normal mice were subcutaneously injected with equivalent volume of saline; in model group, the T2DM mice were subcutaneously injected with equivalent volume of saline; in low-and high-dose liraglutide treatment groups, the T2DM mice were subcutaneously injected with 100 and 200 μg·kg^-1·d^-1, respectively. After 4 weeks of administration, the levels of FBG, TG, TC, HDL-C, LDL-C, ALT and AST were determined. HE staining was used to observe the pathological changes of the liver tissues. The protein level of cleaved caspase-3 in the liver tissue was detected by the technique of immunofluorescence. The protein levels of p-AMPK/AMPK and apoptosis-related proteins were detected by Western blot. The expression of miR-33 in the liver tissues was detected by real-time PCR. RESULTS: Compared with model group, the contents of FBG, TG, TC, LDL-C, ALT and AST were decreased significantly, while the content of HDL-C was increased significantly in low-dose liraglutide group and high-dose liraglutide group (P<0.05). The protein levels of phosphorylated AMPK and Bcl-2 were up-regulated significantly, and the expression of cleaved caspase-3 was down-regulated significantly (P<0.05). The level of miR-33 was decreased significantly (P<0.01). CONCLUSION: Liraglutide alleviates liver injury in type 2 diabetic mice, and the mechanism may be associated with reducing the level of miR-33 and increasing the phosphorylation of AMPK in the liver tissues, thereby inhibiting hepatocyte apoptosis.     

Fucoidan and Cancer: A Multifunctional Molecule with Anti-Tumor Potential

There is a wide variety of cancer types yet, all share some common cellular and molecular behaviors. Most of the chemotherapeutic agents used in cancer treatment are designed to target common deregulated mechanisms within cancer cells. Many healthy tissues are also affected by the cytotoxic effects of these chemical agents. Fucoidan, a natural component of brown seaweed, has anti-cancer activity against various cancer types by targeting key apoptotic molecules. It also has beneficial effects as it can protect against toxicity associated with chemotherapeutic agents and radiation. Thus the synergistic effect of fucoidan with current anti-cancer agents is of considerable interest. This review discusses the mechanisms by which fucoidan retards tumor development, eradicates tumor cells and synergizes with anti-cancer chemotherapeutic agents. Challenges to the development of fucoidan as an anti-cancer agent will also be discussed.     

β-carotene attenuates weaning-induced apoptosis via inhibition of PERK-CHOP and IRE1-JNK/p38 MAPK signalling pathways in piglet jejunum

Weaning may cause oxidative injury, immune response impairment, apoptosis and other injuries in piglets. Oxidative and endoplasmic reticulum stress (ERS) can elicit inflammatory responses, and persistent oxidative and ERS also may lead to apoptotic cascades, which is associated with the pathogenesis of multiple diseases. β-carotene, a natural carotenoid, has potential anti-inflammatory and antioxidant functions. However, the effect of β-carotene on apoptosis in weaned piglets and the detailed molecular mechanism remain unclear. In this study, we found that β-carotene decreased malondialdehyde (MDA) levels and increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in piglet serum. β-carotene could inhibit the mRNA levels of caspase-3 significantly, but had no significant inhibitory effect of the mRNA levels of caspase-9 and caspase-12 in the piglet jejunum. In addition, β-carotene decreased the activation of GRP78, CHOP, and JNK/p38 MAPK and the ratio of Bax/Bcl-2. Furthermore, β-carotene had a significant influence on the activation of ERS and apoptosis-related signals in TG-induced IPEC-J2. In the present study, β-carotene pre-treatment attenuated the ratio of Bax/Bcl-2 and prevented TG-induced increases in the level of PERK-CHOP and IRE1-JNK/p38 MAPK pathway activation in a dose-dependent manner. Overall, these findings indicate that β-carotene may protect weaning-induced apoptosis through inhibiting ERS.