Role of the Central Circulation in Regulation of Cutaneous Gas Exchange

SYNOPSIS. Although primarily limited by the rate of diffusionof oxygen and carbon dioxide across the integument, cutaneousgas exchange is also affected by adjustments in the absoluteflow of blood to the skin, the pattern of distribution of bloodwithin the cutaneous vascular bed, and the effects of centralvascular shunting on gas partial pressures of arterial bloodperfusing the skin. The interplay of these various factors,particularly in animals with heterogeneous arterial supply tothe skin and/or with highly variable intracardiac shunts, potentiallyis complex, only poorly understood, and worthy of considerablefuture experimentation.     

缺氧信号在骨中的核心作用

缺氧信号在维持氧稳态和细胞生存中起着至关重要的作用。在胚胎发育时期处于快速增殖的细胞和肿瘤组织中快速生长的细胞中都能观察到缺氧现象的存在。为了应对缺氧胁迫,生物有机体形成了一系列的调节机制。在多种调节途径中,缺氧诱导因子HIF-1和HIF-2是最主要的能够应答细胞内氧气浓度的降低而对多种基因进行调控的转录因子,与生物体的生长发育及一些疾病的发病机理都存在着密切关系。最近的研究发现在骨骼发育,骨骼的形成和再生,以及关节的形成和动态平衡的调节中HIF-1和HIF-2的具有重要作用。此外,HIF-1和HIF-2的过度表达在临床上与骨肉瘤和骨关节炎明显相关。总之,这些发现预示着缺氧的信号在骨骼的生物学及其疾病中起到中心调节的作用。     

A Role for the Geomagnetic Field in Cell Regulation

We advance the hypothesis that biological systems utilize the geomagnetic field (GMF) for functional purposes by means of ion cyclotron resonance-like (ICR) mechanisms. Numerous ICR-designed experiments have demonstrated that living things are sensitive, in varying degrees, to magnetic fields that are equivalent to both changes in the general magnetostatic intensity of the GMF, as well as its temporal perturbations. We propose the existence of ICR-like cell regulation processes, homologous to the way that biochemical messengers alter the net biological state through competing processes of enhancement and inhibition. In like manner, combinations of different resonance frequencies all coupled to the same local magnetic field provide a unique means for cell regulation. Recent work on ultraweak ICR magnetic fields by Zhadin and others fits into our proposed framework if one assumes that cellular systems generate time-varying electric fields of the order 100 mV/cm with bandwidths that include relevant ICR frequencies.     

Role of the Central Adrenergic System in the Regulation of Prostaglandin Biosynthesis in Rat Brain

The role of endogenous catecholamines in the regulation of brain prostaglandin (PG) synthesis was studied in the rat. Male rats were injected in the brain lateral ventricle or in the ventral noradrenergic bundle with either the catecholaminergic neurotoxin 6-hydroxydopamine or vehicle. Other groups of rats were injected intraperitoneally with the tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine, or with the inhibitor of dopamine-beta-hydroxylase, FLA-63. All these drugs produced a significant depletion of norepinephrine (NE) content in the cortex and hypothalamus. The rats that had lower levels of NE exhibited reduced capacity to synthesize PGE2 but not thromboxane B2 and 6-keto-PGE1 alpha in the cortex and hypothalamus. However, induced production of PG, stimulated by the bacterial endotoxin lipopolysaccharide (LPS), remained unchanged, namely, a similar (2- to 2.5-fold) increase of PG synthesis was noted in control and in NE-depleted rats. We suggest that the regulation of PG synthesis under basal condition requires intact adrenergic input, whereas LPS-induced production of PG is independent of the adrenergic innervation.     

A Role for BK Channels in Heart Rate Regulation in Rodents

The heart generates and propagates action potentials through synchronized activation of ion channels allowing inward Na⁺ and Ca²⁺ and outward K⁺ currents. There are a number of K⁺ channel types expressed in the heart that play key roles in regulating the cardiac cycle. Large conductance calcium-activated potassium (BK) ion channels are not thought to be directly involved in heart function. Here we present evidence that heart rate can be significantly reduced by inhibiting the activity of BK channels. Agents that specifically inhibit BK channel activity, including paxilline and lolitrem B, slowed heart rate in conscious wild-type mice by 30% and 42%, respectively. Heart rate of BK channel knock-out mice (Kcnma1^−/−) was not affected by these BK channel inhibitors, suggesting that the changes to heart rate were specifically mediated through BK channels. The possibility that these effects were mediated through BK channels peripheral to the heart was ruled out with experiments using isolated, perfused rat hearts, which showed a significant reduction in heart rate when treated with the BK channel inhibitors paxilline (1 µM), lolitrem B (1 µM), and iberiotoxin (0.23 µM), of 34%, 60%, and 42%, respectively. Furthermore, paxilline was shown to decrease heart rate in a dose-dependent manner. These results implicate BK channels located in the heart to be directly involved in the regulation of heart rate.     

乙酰转移酶基因NAA10的生物学功能及其在肿瘤中的作用

N端乙酰转移酶A（N-acetyltransferase A, NatA）复合体是真核生物最主要的N端氨基酸α位乙酰转移酶,N端α位乙酰转移酶10基因（N-α-acetyltransferase 10, NAA10）编码的N端α位乙酰转移酶10蛋白（N-α-acetyltransferase 10 protein, Naa10p）是NatA的催化亚基. Naa10p具备新生蛋白质N端氨基酸α位乙酰化活性、成熟蛋白质Lys残基ε位乙酰化活性以及对部分转录因子的协同调节作用. Naa10p能够通过调节细胞周期促进细胞增殖,通过调节雷帕霉素靶蛋白（mechanistic target of rapamycin, mTOR）通路促进细胞自噬,并通过多种不同的分子信号通路抑制细胞运动能力.根据乙酰化底物的不同,Naa10p还在细胞凋亡的调控中起双重作用. Naa10p参与的生物学过程还涉及血管生成和神经发育等. Naa10p在多种癌症组织中呈过表达,但其预后意义随肿瘤不同而有较大差别.对Naa10p的生理生化研究必将使我们对细胞的生理病理学过程及其机制的了解更加深入全面.本文将从蛋白质结构、机制功能及临床意义等不同角度系统地阐述NAA10的研究现状与进展.     

A Novel Role for the Hypoxia Inducible Transcription Factor HIF-1alpha: Critical Regulation of Inflammatory Cell Function

No abstract available.     

MicroRNA:线粒体功能调控的新机制

线粒体是真核生物进行能量代谢的主要场所,在自由基产生、细胞凋亡、衰老等生理病理活动中也起到重要作用。线粒体功能受核基因和线粒体基因共同调控,microRNA(miRNA)介导的基因转录后调控是重要机制之一。核基因编码的miRNA不仅可以通过调控核基因编码的线粒体相关蛋白的表达影响线粒体结构和功能,而且可以进入线粒体并调控线粒体基因的表达。另一方面,线粒体基因也可能编码miRNA,直接调控线粒体基因表达或转运至胞质调控核基因的表达。