Endoplasmic Nuclear membrane

Many of the morphological and biochemical changes that occur in cells that die by necrosis are very different from those that occur in apoptosis. During necrosis cells swell, mitochondria and endoplasmic reticulum lose their structure and become dysfunctional and the nuclear membrane becomes disrupted (Fig. 35-1). Necrotic death is independent of premitochondrial apoptotic proteins such as Bax, cytochrome c release and caspase activation. Necrosis is further distinguished from apoptosis by the fact that necrosis usually occurs as the result of a traumatic physical injury or stroke and cells die en masse, whereas apoptosis typically occurs in individual cells within a population of surviving neighbors. 

The nucleus is separated from the cytoplasm by the nuclear envelope, which consists of the outer and inner nuclear membranes. Each of the two nuclear membranes has two layers, and the membranes are separated from each other by the perinuclear space. The outer nuclear membrane is continuous with the rough endoplasmic reticulum and is covered with ribosomes. The inner side of the membrane is covered with a protein layer (the nuclear lamina), in which the nuclear structures are anchored. 

The most important membranes in animal cells are the plasma membrane, the inner and outer nuclear membranes, the membranes of the endoplasmic reticulum (ER) and the Golgi apparatus, and the inner and outer mitochondrial membranes. Lysosomes, peroxisomes, and various vesicles are also separated from the cytoplasm by membranes. In plants, additional membranes are seen in the plastids and vacuoles. All membranes show polarity—e., there is a difference in the composition of the inner layer (facing toward the cytoplasm) and the outer layer (facing away from it). 

The endoplasmic reticulum (ER) is an extensive closed membrane system consisting of tubular and saccular structures. In the area of the nucleus, the ER turns into the external nuclear membrane. Morphologically, a distinction is made between the rough ER (rER) and the smooth ER (sER). Large numbers of ribosomes are found on the membranes of the rER, which are lacking on the sER. On the other hand, the sER is rich in membrane-bound enzymes, which catalyze partial reactions in the lipid metabolism as well as biotransformations. 

Cytochromes P-450 may be found in other organelles as well as the SER including the rough endoplasmic reticulum and nuclear membrane. In the adrenal gland, it is also found in the mitochondria, although here adrenodoxin and adrenodoxin reductase are additional requirements in the overall system. Although the liver has the highest concentration of the enzyme, cytochromes P-450 are found in most, if not all, tissues. 

Five kinds of phospholipid predominate phosphatidylcholine, phosphatidylethanolamine, phosphatidyl-serine, phosphatidylglycerols, and sphingomyelin. Usually there are also small amounts of phosphatidyli-nositol. The major phospholipid in animal cells is phosphatidylcholine, but in bacteria it is phosphatidylethanolamine. The phospholipids of E. coli consist of 80% phosphatidylethanolamine, 15% phosphati-dylglycerol, and 5% diphosphatidylglycerol (cardio-lipin). Significant amounts of cardiolipin are found only in bacteria and in the inner membrane of mitochondria. Sphingomyelin is almost absent from mitochondria, endoplasmic reticulum, or nuclear membranes. 

Endoplasmic reticulum 0.007-0.01 Highly invaginated membrane or set of tubules, probably connected with both the cell membrane and the nuclear membrane and concerned in protein synthesis and probably other metabolic functions... 

Distribution of CYPs within the cell has been studied primarily in the mammalian liver, where it is present in greatest quantity in the smooth endoplasmic reticulum and in smaller but appreciable amounts in the rough endoplasmic reticulum. The nuclear membrane has also been reported to contain CYP and to have detectable aryl hydrocarbon hydroxylase activity, an observation that may be of considerable importance in studies of the metabolic activation of carcinogens. 

Matthyssee and Phillips (20) isolated two nuclear proteins, from tobacco cells, that bound specifically to 2,4-D. Receptor proteins for auxins, kinetins, and GA have been found (21). Sub-cellular fractions from bean leaves were recently shown to bind abscisic acid (22). Preliminary experiments (22) indicated that maximum ABA binding activity coincides with the activities of membrane-bound Mg -dependent, K+-stimulated ATPase and glucan synthetase. Table I of Biswas and Roy (21) lists hormone receptor proteins reported in plant tissue. For a protein to qualify as a receptor molecule, it should have a high stereo-specific binding capacity (Kd 10 6 to 10 SM) for its particular hormone. In com coleoptiles, both IAA and NAA are equally effective in inducing cell elongations fractions of plasma membrane and endoplasmic reticular membrane contain receptor proteins with Kd values of 10 M to 10 M for auxins (5, 18). When one considers procedural... 

Members of the Bcl-2 family share one or more Bcl-2 homology (BFI) domains, named BFI1, BFI2, BFI3, and BFI4 (Adams and Cory, 1998). It is not yet clear which structural features determine if these proteins possess pro- or anti-apoptotic activities. However, some studies revealed that the BH3 domain is a critical domain for the proapoptotic members (Chittenden et al., 1995). Besides BH domains, some contain a hydrophobic domain in the C-terminal region, which is essential for the attachment to intracellular membranes, like the outer mitochondrial, nuclear, and endoplasmic reticulum membranes (Krajewski et al., 1993 Nguyen et al., 1993). 

The third strategy is used by viruses whose nucleocapsids are produced in the nucleus of the cell, with assembly and maturation involving the nuclear membrane. The enveloped viruses accumulate in the endoplasmic reticulum and are carried to the cell surface via vacuoles. Some viruses that use this process, such as herpesvirus, are cytolytic (cause cell lysis). 

The nucleus of the cell (Figure 1.2) is composed of a porous nuclear membrane, the nucleolus, and soluble materials. The nucleolus contains ribonucleic acids (RNA) and genetic materials also termed chromatin that code for the proteins synthesized upon the ribosomes in the cell cytoplasm. The nuclear membrane is continuous with the outer membrane of the endoplasmic reticulum. Messenger RNA synthesized in the nucleus is transported across the nuclear membrane and is involved in protein synthesis. It fits into the groove between the large and small rRNA subunits (Figure 1.2)... 

Microsomal epoxide hydrolase is widely distributed, having been described from plants, invertabrates, and vertebrates. In vertebrates it has wide organ distribution for example, in the rat, the most studied species, the enzyme has been found in essentially every organ and tissue. Although predominantly located in the endoplasmic reticulum (microsomes), epoxide hydrolase is also found in the plasma and nuclear membranes and, to some extent, in the cytosolic fraction. 

SREBPs are transcription factors that bind to the sterol regulatory element DNA sequence TCACNCCAC. Unactivated SREBPs are attached to the nuclear envelope and endoplasmic reticulum membranes. In cells with low levels of sterols, SREBPs are cleaved to a water-soluble N-terminal domain that is translocated to the nucleus. These activated SREBPs then bind to specific sterol regulatory element DNA sequences, thus up-regulating the synthesis of enzymes involved in sterol biosynthesis. Sterols in turn inhibit the cleavage of SREBPs and therefore synthesis of additional sterols is reduced through a negative-feedback loop. 

Fig. 2.18 Nucleus, nucleolus and hyaloplasm of the liver cell (20) cell nucleus (CN), marginal nucleolus (N), electron-dense dark nuclear capsule (DC), undulating nuclear membrane with (partial) fusion of the two membranes (NM), endoplasmic reticulum (ER), mitochondria (M) X 14,600...

In the cytoplasm, the endoplasmic reticulum is a complex system of double membranes with a lumen —20 nm wide. These membranes are so fine that they are only visible by electron microscopy. They are probably associated with nearly every organelle, having connections with the nuclear membrane, the plasmalemma, and the mitochondria (for a review, see Ref. 93). It would be surprising were the endoplasmic reticulum not an important structure for metabolic compartmentation. 

The answer is c. (Murray, pp 452—467. Scriver, pp 3—45. Sack, pp 1—40. Wilson, pp 101-120.) Prokaryotic ribosomes have a sedimentation coefficient of 70S and are composed of SOS and 30S subunits. Eukaryotic cytoplasmic ribosomes, either free or bound to the endoplasmic reticulum, are larger—60S and 40S subunits that associate to an SOS ribosome. Nuclear ribosomes are attached to the endoplasmic reticulum of the nuclear membrane. Ribosomes in chloroplasts and mitochondria of eukaryotic cells are more similar to prokaryotic ribosomes than to eukaryotic cytosolic ribosomes. Like bacterial ribosomes, chloroplast and mitochondrial ribosomes use a formylated tRNA. In addition, they are sensitive to many of the inhibitors of protein synthesis in bacteria. 

---