Autophagy: Mechanisms, regulation, and its role in tumorigenesis

Autophagy (from Greek “auto” — self, “phagos” — to eat) is the major catabolic process involved in the delivery and lysosomal degradation of long-lived intracellular components: proteins, lipids, nucleic acids, and organelles. Since the discovery of genes involved in regulation of autophagy in the 1990s, there has been a significant increase in studies of autophagy as a process involved in maintaining cellular homeostasis, as well as its role in the development of different pathologies. This review focuses on the basics of autophagy and its regulatory mechanisms. The role of autophagy in the maintenance of cellular homeostasis and tumorigenesis is also discussed.     

Hemostatic regulation and Whitehead's philosophy of organism

Biology as a scientific discipline has relied heavily upon advances in chemistry and physics. An inherent danger in this relationship is the reduction of living phenomena to physico-chemical terms. Whitehead's Philosophy of Organism is utilized to examine current methodologies within biology and to evaluate their appropriateness for future research. Hemostatic regulation is employed to illustrate the applications of organistic concepts to biological research. It is concluded that understanding of living entities and their properties as well as possibly life itself will require synthesis of the many analytical elements as informational structures.     

Neurotensin: physiological properties and role in the regulation of organism function

In review one can find summarized data about neurotensin structure, properties and physiological activity, presented in publications of last 30 years, from the time when this peptide has been discovered. The article contains data about neurotensin blood plasma level and its distribution in various organs and tissues in humans and different animal species. Main manifestations of neurotensin physiological activity are discussed as its participation in regulation of cardiovascular, digestive and endocrine systems and also in regulation of immunity and cell growth. From clinical point of view, obvious interest represents neurotensin ability to produce neuroleptical and antipsychotie effects after injecting into the brain ventricles.     

Mechanisms and regulation of the programmed cell death

The programmed cell death usually is identified with apoptosis, though a scheduled sequence of events can be observed also in autophagy, mitotic catastrophe and, under certain circumstances, in necrosis. Apoptosis begins with activation of the initiator caspases (cysteine proteases) in the signaling complexes: the apoptosome (on the intrinsic or mitochondrial pathway) or the degradosome (on the extrinsic or death receptor pathway). The proteolytic cascade then leads, through activation of downstream caspases and DNases, to digestion of cell components. Mitochondria play a central role in apoptosis by releasing cytochrome c--the essential component of the apoptosome, Smac/Diablo and OmiI/HtrA2--that bind the caspase inhibitors (IAPs), and endonuclease G and AIF--that are responsible for DNA degradation. Those factors get out of mitochondrium through the Bax and Bak protein-containing channels. The process is fast and complete, probably due to mechanoenzyme--driven remodeling of the organellum structure as well as to phospholipid peroxidation and proteolysis in the inner membrane. The release of the mitochondrial factors can be stimulated by protein p53, histone H1.2 and poly(ADP-ribose) that are sent from the nucleus in consequence of a cyto- and genotoxic stress, under the control of cAbl kinase.     

20-羟二十烷四烯酸在机体生理及病理调节中的作用

20多年前,国外学者就报道了机体内某些组织中存在着细胞色素P-450（cytochrome P-450,CYP）。已经证实它能催化花生四烯酸（arachidonic acid,AA）的ω-羟基生成20-羟二十烷四烯酸（20-hydroxyeicosatetraenoic acid,20-HETE）。随着研究的不断深入,人们逐渐发现作为第二信使,20-HETE在调节血管平滑肌紧张度、肾功能、脑血流量和肺血管舒张过程中发挥了重要作用;外源性的20-HETE对心脏冠脉循环也有明显的调节作用;并且它与高血压和妊娠毒血症等疾病的发生和发展关系密切。但国内对于20-HETE的相关研究还鲜有报道,本文将主要就20-HETE在机体生理及病理及病理调节中的作用作一综述。     

Mechanisms and regulation of autophagosome formation

Autophagy is an intracellular pathway for the bulk degradation of cytoplasmic substances such as cytosol, protein aggregates and organelles. Autophagy is characterized by the formation of double-membrane bound vesicles called autophagosomes, which engulf the cargo and transport it to the vacuole/lysosome for breakdown and recycling. Even though several proteins in this pathway have been identified, little is known about the mechanism of action of these proteins during autophagosome biogenesis. In this review we briefly discuss recent findings on the molecular players and mechanisms involved in autophagosome formation. In particular, we will focus on the mechanisms regulating membrane recruitment as well as membrane remodeling during autophagosome formation.     

Problem of organism integrity and its perspectives

The organism integrity in onto-and phylogenesis is considered as an initial element of biosphere integrity and its evolution at the eukaryotic level. The Schmalhausen’s concept of organism integrity is discussed in the context of his original strategy of evolutionary synthesis and his works on stabilizing selection. The perspectives of investigations on the problem of integrity and development of the principle of dynamic stability in contemporary evolutionary biology as integrating factors are discussed.     

Mechanisms in the regulation of aromatase in developing ovary and placenta

During human gestation, the placental syncytiotrophoblast develops the capacity to synthesize large amounts of estrogen from C₁₉-steroids secreted by the fetal adrenals. The conversion of C₁₉-steroids to estrogens is catalyzed by aromatase P450 (P450arom), product of the CYP19 gene. The placenta-specific promoter of the hCYP19 gene lies 100,000 bp upstream of the translation initiation site in exon II. In studies using transgenic mice and transfected human trophoblast cells we have defined a 246-bp region upstream of placenta-specific exon I.1 that mediates placental cell-specific expression. Using transgenic mice, we also observed that as little as 278 bp of DNA flanking the 5′-end of ovary-specific hCYP19 exon IIa was sufficient to target ovary-specific expression. This ovary-specific promoter contains response elements that bind cAMP-response element-binding protein (CREB) and the orphan nuclear receptors SF-1 and LRH-1, which are required for cAMP-mediated stimulation of CYP19 expression in granulosa and luteal cells during the estrous cycle and pregnancy. In this article, we review our studies to define genomic regions and response elements that mediate placenta-specific expression of the hCYP19 gene. The temporal and spatial expression of LRH-1 versus SF-1 in the developing gonad during mouse embryogenesis and in the postnatal ovary also will be considered.