铁死亡：一种新的细胞死亡方式

死亡不仅是所有细胞的最终命运,而且它与细胞分裂、增殖一样,在整个机体的生长、发育中具有不可替代的作用.目前认为,除了坏死外,细胞死亡形式分为程序性细胞死亡(programmedcell death,PCD),包括凋亡(apoptosis)和自噬(autophagy),及非程序性细胞死亡(non-programmedcell death,NPCD),包括副凋亡(paraptosis)、细胞有丝分裂灾难(mitotic catastrophe)和胀亡(oncosis)     

A Model of Blebbing in Mitotic Tissue Culture Cells

A preliminary study of blebbing in tissue cultures has been made. The tubal epithelium of fetal mouse oviduct was cultured at 37°C in Rose chambers. A cinematographic record was obtained of phase microscope observations of mitotic cells. Measurements of the size of both cells and blebs were made on the film using a “traveling” microscope. The duration and the rise and decay times of blebs were determined simply by counting frames on the film. Detailed observations are reported on blebbing in four cells undergoing mitosis. The results indicate that the frequency of blebbing as well as the duration of individual blebs exhibits a maximum during telophase. A model is proposed to account for blebbing in mitotic cells. The model attributes to local regions of the cell membrane the property of constant tension independent of stretch over some restricted range of stretch. This property implies that the cell membrane is locally unstable. Further assumptions stated explicitly in the model are that (i) cell division occurs at constant volume, (ii) the cell membrane stretches during cleavage, (iii) there is a positive pressure drop across the cell membrane. Evidence is cited in support of these assumptions as well as independent evidence that the cell membrane may be locally unstable. A physical model is described which would be expected to exhibit blebbing given the above assumptions.     

Self-Protection against Cell Wall Hydrolysis in Streptococcus milleri NMSCC 061 and Analysis of the Millericin B Operon

Streptococcus milleri NMSCC 061 produces an endopeptidase, millericin B, which hydrolyzes the peptide moiety of susceptible cell wall peptidoglycan. The nucleotide sequence of a 4.9-kb chromosomal region showed three open reading frames (ORFs) and a putative tRNA^Leu sequence. The three ORFs encode a millericin B preprotein (MilB), a putative immunity protein (MilF), and a putative transporter protein (MilT). The milB gene encodes a 277-amino-acid preprotein with an 18-amino-acid signal peptide with a consensus IIGG cleavage motif. The predicted protein encoded by milT is homologous to ABC (ATP-binding cassette) transporters of several bacteriocin systems and to proteins implicated in the signal-sequence-independent export of Escherichia coli hemolysin A. These similarities strongly suggest that the milT gene product is involved in the translocation of millericin B. The gene milF encodes a protein of 302 amino acids that shows similarities to the FemA and FemB proteins of Staphylococcus aureus, which are involved in the addition of glycine to a pentapeptide peptidoglycan precursor. Comparisons of the cell wall mucopeptide of S. milleri NMSCC 061(resistant to lysis by millericin B) and S. milleri NMSCC 051(sensitive) showed a single amino acid difference. Serial growth of S. milleri NMSCC 051 in a cell wall minimal medium containing an increased concentration of leucine resulted in the in vivo substitution of leucine for threonine in the mucopeptide of the cell wall. A cell wall variant of S. milleri NMSCC 051 (sensitive) that contained an amino acid substitution (leucine for threonine) within its peptidoglycan cross bridge showed partial susceptibility to millericin B. The putative tRNA^Leu sequence located upstream of milB may be a cell wall-specific tRNA and could together with the milF protein, play a potential role in the addition of leucine to the pentapeptide peptidoglycan precursor and thereby, contributing to self-protection to millericin B in the producer strain.     

Topotaxis: A New Mechanism of Directed Cell Migration in Topographic ECM Gradients

Living cells orient the cytoskeleton polarity and directional migration in response to spatial gradients of multiple types of cues. The resulting tactic behaviors are critical for the proper cell localization in the context of complex single-cell and tissue behaviors. In this perspective, we highlight the recent discovery of, to our knowledge, a new -taxis phenomenon, the topotaxis, which mediates directional cell migration in response to the gradients of such topographic features as the density of extracellular matrix fibers. The direction of topotactic migration critically depends on the effective stiffness of the cortical cytoskeleton, which is controlled by the balance between two parallel signaling pathways activated by the extracellular matrix input. Topotaxis can account for such striking cell behaviors as the opposite directionality of migration of benign and metastatic cancer cells and certain aspects of the wound-healing process. We anticipate that, in conjunction with other tactic phenomena, topotaxis can provide critical information for understanding and design of tissue structure and function.     

自噬的分子细胞机制研究进展

自噬是真核细胞中进化上高度保守的、用于降解和回收利用细胞内生物大分子和受损细胞器的过程。自噬的完成依赖于正常的溶酶体功能,与机体的多种生理和病理过程密切相关。自噬研究已成为当前生命科学研究的热点,揭示自噬的发生机制、自噬与疾病发生的关系对预防与治疗多种人类重大疾病具有重要意义。该文旨在概括目前自噬的研究进展,重点介绍细胞自噬的发生机制及其与疾病的关系。     

Cell Swelling, Blebbing, and Death Are Dependent on ATP Depletion and Independent of Calcium During Chemical Hypoxia in a Glial Cell Line (ROC-1)

The morphological and biochemical changes that occur during chemical hypoxic injury in a neural cell line were studied in the presence and absence of calcium. Oligodendroglial-glioma hybrid cells (ROC-1) were subjected to inhibitors of glycolytic and oxidative ATP synthesis (chemical hypoxia). Complete respiratory inhibition depleted [ATP] to less than 5% of control by 4 min. Blebs appeared on the cell surfaces and cells began to swell within a few minutes of ATP depletion. A 200% increase in cell volume and bleb coalescence preceded irreversible cell injury (lactate dehydrogenase release) which began at approximately 20 min with 50% cell death by 40 min. In energized cells an equivalent degree of osmotic swelling induced by ouabain inhibition of the Na+, K(+)-ATPase pump did not produce blebbing or cell death. Partial inhibition of respiration decreased [ATP] to approximately 10% of control by 40 min. Blebbing and swelling began at 40 min and bleb coalescence preceded plasma membrane disruption which began at approximately 55 min. ATP depletion, blebbing, swelling, and death followed similar time courses in the presence or absence of extracellular calcium ([Ca2+]e). Intracellular calcium ([Ca2+]i) was measured using fura-2. In calcium-containing medium metabolic inhibition caused a transient increase in resting [Ca2+]i (100 +/- 17 nM) followed by a low steady-state level preceding plasma membrane disruption. Following deenergization in calcium-free medium, [Ca2+]i remained below 60 nM throughout injury and death. These data suggest that decreased ATP initiates a sequence of events including bleb formation and cell swelling that lead to irreversible cell injury in the absence of large increases in [Ca2+]i.     

Stress‐Induced Evolutionary Innovation: A Mechanism for the Origin of Cell Types

Understanding the evolutionary role of environmentally induced phenotypic variation (i.e., plasticity) is an important issue in developmental evolution. A major physiological response to environmental change is cellular stress, which is counteracted by generic stress reactions detoxifying the cell. A model, stress‐induced evolutionary innovation (SIEI), whereby ancestral stress reactions and their corresponding pathways can be transformed into novel structural components of body plans, such as new cell types, is described. Previous findings suggest that the cell differentiation cascade of a cell type critical to pregnancy in humans, the decidual stromal cell, evolved from a cellular stress reaction. It is hypothesized that the stress reaction in these cells was elicited ancestrally via inflammation caused by embryo attachment. The present study proposes that SIEI is a distinct form of plasticity‐based evolutionary change leading to the origin of novel structures rather than adaptive transformation of pre‐existing characters.     

低温保护剂加入/取出过程中细胞体积的极值

低温保护剂是细胞低温保存过程中必不可少的,其加入／取出过程受到细胞体积变形极限的限制．在两参数细胞渗透模型的基础上,得到了细胞在低温保护剂加入／取出过程中细胞内水体积和细胞体积极值的解析解,分析了低温保护剂的渗透性和初始浓度差对细胞体积极值的影响。     

Cell Fate Regulation upon DNA Damage: p53 Serine 46 Kinases Pave the Cell Death Road

Mild and massive DNA damage are differentially integrated into the cellular signaling networks and, in consequence, provoke different cell fate decisions. After mild damage, the tumor suppressor p53 directs the cellular response to cell cycle arrest, DNA repair, and cell survival, whereas upon severe damage, p53 drives the cell death response. One posttranslational modification of p53, phosphorylation at Serine 46, selectively occurs after severe DNA damage and is envisioned as a marker of the cell death response. However, the molecular mechanism of action of the p53 Ser46 phospho‐isomer, the molecular timing of this phosphorylation event, and its activating effects on apoptosis and ferroptosis still await exploration. In this essay, the current body of evidence on the molecular function of this deadly p53 mark, its evolutionary conservation, and the regulation of the key players of this response, the p53 Serine 46 kinases, are reviewed and dissected.     

Effect of Chilling Temperatures upon Cell Cultures of Tomato

The effect of chilling temperatures upon cell cultures of tomato (Lycopersicon esculentum Mill cv `VF36,' and cv `VFNT Cherry,' and L. hirsutum Humb. & Bonpl.) was tested. Doubling times for L. esculentum were 2 to 3 days at 28°C, and 3 to 8 days at 12°C. No growth was observed at 8°C, indicating an abrupt limit to growth between 8 and 12°C. Fluorescein diacetate staining indicated that 80 to 90% of the cells were alive when cells were maintained at 8°C for up to 2 weeks. When cultures kept at 8°C for up to 30 days were transferred to 28°C, growth resumed quickly, and at a rate virtually identical to that for unchilled cells. Similar results were found for cells maintained at 0°C, and for cells of `VFNT Cherry' and of L. hirsutum. Under certain conditions, cultures slowly doubled in fresh weight and cell volume at 8 or 9°C but additional growth at 8°C did not occur, nor could growth be maintained by subculture at 8 or 9°C. The results are contrary to reports that cell cultures of tomato die when exposed to temperatures below 10°C for 1 or 2 weeks. Our observations indicate that chilling temperatures quickly inhibit growth of tomato cells, but do not kill them.     

Cell death upon epigenetic genome methylation: a novel function of methyl-specific deoxyribonucleases

Background  

Alteration in epigenetic methylation can affect gene expression and other processes. In Prokaryota, DNA methyltransferase genes frequently move between genomes and present a potential threat. A methyl-specific deoxyribonuclease, McrBC, of Escherichia coli cuts invading methylated DNAs. Here we examined whether McrBC competes with genome methylation systems through host killing by chromosome cleavage.     

Mechanism of caspase-2 activation upon DNA damage

The mechanism of caspase-2 activation in response to DNA damage was studied using human ovarian cancer cells Caov-4 treated with chemotherapeutic agent cisplatin. It was shown that mutations of the three cleavage sites of caspase-2 do not affect the assembly of the macromolecular complex of caspase-2 and its activation, but, conversely, stabilize this complex, most likely, via the inhibition of the dissociation of the active caspase-2.