Liver Diseases
George Feuer, Felix A. de la Iglesia in Molecular Biochemistry of Human Disease, 2020
The liver is one of our vital organs; it has several roles which include metabolic, synthetic, secretory, and excretory functions. In the fetus it is a hematopoietic organ, and a processing, storage, and defense organ throughout our lifespan. The liver operates like a complex chemical factory, producing many essential blood proteins and lipids, metabolizing foodstuffs and foreign compounds, altering and synthesizing new substances, and regulating plasma concentrations of many molecules. Diseases of the liver are related to one or more functions; changes in the biochemical bases of these functions, therefore, lead to hepatic ailments. The control of synthesis and metabolism represents the maintenance of homeostasis. The integrity of the plasma membrane structure is essential for the maintenance of normal hepatic functions. The importance of membrane structure in relation to hepatobiliary disease is mostly concerned with the endoplasmic reticulum and the plasma membrane.
Structure and function of skin
Roger L. McMullen in Antioxidants and the Skin, 2018
This chapter attempts to cover some of the fundamental concepts involving the structure and function of skin. It discusses the Skin Immune System and various cells associated with the immune response are found. Morphologically, the skin is composed of two principal components, the epidermis and dermis, which contain various cell types and structural proteins. The stratum basale is the lowest layer in the epidermis and consists of a single layer of cells, which are predominantly keratinocytes. In this part of the epidermis, the keratinocytes are undifferentiated and contain all of the usual organelles that are present in viable cells, such as mitochondrion, Golgi apparatus, ribosome, endoplasmic reticulum, lysosome, and nucleus. The primary cell types present in the dermis include fibroblasts, mast cells, and tissue macrophages. Fibroblasts are the most abundant cell type and are responsible for the synthesis and structuring of the structural tissue and ground substance.
Hyperglycemia Impairs Blood Vessel Function
Robert Fried, Richard M. Carlton in Type 2 Diabetes, 2018
This chapter describes the steady process whereby oxidative stress leads to Type 2 diabetes, and damages vascular endothelium, by causing loss of nitric oxide (NO) synthesis. This loss results in both micro- and macrovessel damages as commonly seen in neuro- and vasculopathies present in many organs ranging from the eyes to the kidneys. The chapter also cites the evidence for endoplasmic reticulum, and mitochondrial stress in vasculopathies resulting from oxidative stress. Here also is a detailed discussion of various means of analysis permitting evaluation of damage due to diabetes. These include clinical correlates of arterial pulse waveform, and velocity, and flow-mediated vasodilation and reactive hyperemia.
Functional knock down of VCAM1 in mice mediated by endoplasmatic reticulum retained intrabodies
Published in mAbs, 2014
Andrea LJ Marschall, Frank N Single, Katrin Schlarmann, Andreas Bosio, Nina Strebe, Joop van den Heuvel, André Frenzel, Stefan Dübel
Functional knockdowns mediated by endoplasmatic reticulum-retained antibodies (ER intrabodies) are a promising tool for research because they allow functional interference on the protein level. We demonstrate for the first time that ER intrabodies can induce a knock-down phenotype in mice. Surface VCAM1 was suppressed in bone marrow of heterozygous and homozygous ER intrabody mice (iER-VCAM1 mice). iER-VCAM1 mice did not have a lethal phenotype, in contrast to the constitutive knockout of VCAM1, but adult mice exhibited physiological effects in the form of aberrant distribution of immature B-cells in blood and bone marrow. The capability to regulate knock-down strength may spark a new approach for the functional study of membrane and plasma proteins, which may especially be valuable for generating mouse models that more closely resemble disease states than classic knockouts do.
Systematic alteration of apoptosis: a review with ultrastructural observations on leukemia cells in vivo
Published in Ultrastructural Pathology, 2018
Yong-Xin Ru, Shi-Xuan Zhao, Shu-Xu Dong, Hao-yue Liang, Ying Wang
The ultrastructural characteristics of apoptosis have been described microscopically for four decades. Alterations of nuclei, apoptotic bodies, cytoplasm, and some organelles have been illustrated and investigated during apoptosis. The successive changes of cellular components corresponding with differentiation of apoptotic cells are illustrated in the present review, based on ultrastructural observation of leukemia cells of patients in our routine clinic work by transmission electron microscopy. Most electron micrographs demonstrated that membranous components of nuclear envelop, rough endoplasmic reticulum and Golgi apparatus, and mitochondria were degenerated step by step during apoptosis. The successive images suggested that the endoplasmic reticulum and Golgi apparatus were transferred to cell surface from cytoplasm and participated in formation of apoptotic bodies in apoptosis, although relevant clinical data and more experimental evidence were needed for restraining of leukemia cases from diagnostic work randomly in recent decades.
Cytochrome c: A Crosslink between the Mitochondria and the Endoplasmic Reticulum in Calcium-Dependent Apoptosis
Published in Cancer Biology & Therapy, 2004
Shulin Wang, Wafik S. El-Deiry
Early and pivotal events in apoptosis are now known to occur in the mitochondria and the endoplasmic reticulum, and release of cytochrome c from the mitochondria and calcium from the endoplasmic recticulum into the cytosol are considered to be requisites for apoptosis in response to different stimuli. In the December 2003 issue of Nature Cell Biology, Boehning et al. report that early in apoptosis mitochondrial cyctochrome c translocates to the endoplasmic reticulum where it specifically binds inositol (1,4,5) triphosphate receptors, leading to sustained calcium release. The released calcium then triggers a mass exodus of cytochrome c from all mitochondria in the cells, thus amplifying the apoptotic signal.