The cell is the basic structural and biological unit of all known living organisms. A cell is the smallest unit of life that can replicate independently, the study of cells is called cell biology. Cells consist of cytoplasm enclosed within a membrane, which contains many such as proteins. Organisms can be classified as unicellular or multicellular, while the number of cells in plants and animals varies from species to species, humans contain more than 10 trillion cells. Most plant and animal cells are only under a microscope. The cell was discovered by Robert Hooke in 1665, who named the unit for its resemblance to cells inhabited by Christian monks in a monastery. Cells emerged on Earth at least 3.5 billion years ago, Cells are of two types, which contain a nucleus, and prokaryotic, which do not. Prokaryotes are single-celled organisms, while eukaryotes can be either single-celled or multicellular, prokaryotic cells were the first form of life on Earth, characterised by having vital biological processes including cell signaling and being self-sustaining.
They are simpler and smaller than eukaryotic cells, and lack membrane-bound organelles such as the nucleus, prokaryotes include two of the domains of life and archaea. The DNA of a prokaryotic cell consists of a chromosome that is in direct contact with the cytoplasm. The nuclear region in the cytoplasm is called the nucleoid, most prokaryotes are the smallest of all organisms ranging from 0.5 to 2.0 µm in diameter. Though most prokaryotes have both a cell membrane and a wall, there are exceptions such as Mycoplasma and Thermoplasma which only possess the cell membrane layer. The envelope gives rigidity to the cell and separates the interior of the cell from its environment, the cell wall consists of peptidoglycan in bacteria, and acts as an additional barrier against exterior forces. It prevents the cell from expanding and bursting from osmotic pressure due to a hypotonic environment, some eukaryotic cells have a cell wall. Inside the cell is the region that contains the genome, ribosomes. The genetic material is found in the cytoplasm.
Prokaryotes can carry extrachromosomal DNA elements called plasmids, which are usually circular, linear bacterial plasmids have been identified in several species of spirochete bacteria, including members of the genus Borrelia notably Borrelia burgdorferi, which causes Lyme disease. Though not forming a nucleus, the DNA is condensed in a nucleoid, plasmids encode additional genes, such as antibiotic resistance genes
In biochemistry and pharmacology, a receptor is a protein molecule that receives chemical signals from outside a cell. When such chemical signals bind to a receptor, they cause some form of cellular/tissue response, sometimes in pharmacology, the term is used to include other proteins that are drug targets, such as enzymes and ion channels. Receptor proteins can be classified by their location, transmembrane receptors include ion channel-linked receptors, G protein-linked hormone receptors, and enzyme-linked hormone receptors. Intracellular receptors are found inside the cell, and include cytoplasmic receptors. The endogenously designated -molecule for a receptor is referred to as its endogenous ligand. E. g. the endogenous ligand for the acetylcholine receptor is acetylcholine but the receptor can be activated by nicotine. Each receptor is linked to a specific cellular biochemical pathway, while numerous receptors are found in most cells, each receptor will only bind with ligands of a particular structure, much like how locks will only accept specifically shaped keys.
When a ligand binds to its receptor, it activates or inhibits the receptors associated biochemical pathway. The ligand-binding cavities are located at the interface between the subunits, type 2, G protein-coupled receptors – This is the largest family of receptors and includes the receptors for several hormones and slow transmitters e. g. dopamine, metabotropic glutamate. They are composed of seven transmembrane alpha helices, the loops connecting the alpha helices form extracellular and intracellular domains. The aforementioned receptors are coupled to different intracellular effector systems via G proteins, the insulin receptor is an example. Type 4, Nuclear receptors – While they are called nuclear receptors, they are located in the cytoplasm. They are composed of a C-terminal ligand-binding region, a core DNA-binding domain, the core region has two zinc fingers that are responsible for recognizing the DNA sequences specific to this receptor. The N terminus interacts with other transcription factors in a ligand-independent manner.
Steroid and thyroid-hormone receptors are examples of such receptors, membrane receptors may be isolated from cell membranes by complex extraction procedures using solvents, and/or affinity purification. The structures and actions of receptors may be studied by using methods such as X-ray crystallography, NMR, circular dichroism. Computer simulations of the behavior of receptors have been used to gain understanding of their mechanisms of action. Ligand binding is an equilibrium process, ligands bind to receptors and dissociate from them according to the law of mass action
The endoplasmic reticulum is a type of organelle in eukaryotic cells that forms an interconnected network of flattened, membrane-enclosed sacs or tube-like structures known as cisternae. The membranes of the ER are continuous with the nuclear membrane. The endoplasmic reticulum occurs in most types of cells, including Giardia. There are two types of endoplasmic reticulum and smooth, the outer face of the rough endoplasmic reticulum is studded with ribosomes that are the sites of protein synthesis. The rough endoplasmic reticulum is especially prominent in such as hepatocytes. The smooth endoplasmic reticulum lacks ribosomes and functions in lipid manufacture and metabolism, the production of steroid hormones, the smooth ER is especially abundant in mammalian liver and gonad cells. The lacy membranes of the endoplasmic reticulum were first seen in 1945 using electron microscopy, the lacy membranes of the endoplasmic reticulum were first seen in 1945 by Keith R. Porter, Albert Claude, Brody Meskers and Ernest F.
Fullam, using electron microscopy. The word reticulum, which network, was applied to describe this fabric of membranes. The general structure of the reticulum is a network of membranes called cisternae. These sac-like structures are held together by the cytoskeleton, the phospholipid membrane encloses the cisternal space, which is continuous with the perinuclear space but separate from the cytosol. The functions of the reticulum can be summarized as the synthesis and export of proteins and membrane lipids. The quantity of both rough and smooth endoplasmic reticulum in a cell can slowly interchange from one type to the other, transformation can include embedding of new proteins in membrane as well as structural changes. Changes in protein content may occur without noticeable structural changes, the surface of the rough endoplasmic reticulum is studded with protein-manufacturing ribosomes giving it a rough appearance. The binding site of the ribosome on the endoplasmic reticulum is the translocon.
However, the ribosomes are not a part of this organelles structure as they are constantly being bound. A ribosome only binds to the RER once a specific protein-nucleic acid complex forms in the cytosol and this special complex forms when a free ribosome begins translating the mRNA of a protein destined for the secretory pathway. The first 5-30 amino acids polymerized encode a signal peptide, a message that is recognized. Translation pauses and the complex binds to the RER translocon where translation continues with the nascent protein forming into the RER lumen and/or membrane
The thyroid hormones and its prohormone, are tyrosine-based hormones produced by the thyroid gland that are primarily responsible for regulation of metabolism. T3 and T4 are partially composed of iodine, a deficiency of iodine leads to decreased production of T3 and T4, enlarges the thyroid tissue and will cause the disease known as simple goitre. The major form of hormone in the blood is thyroxine. In humans, the ratio of T4 to T3 released into the blood is between 14,1 and 20,1, T4 is converted to the active T3 within cells by deiodinases. These are further processed by decarboxylation and deiodination to produce iodothyronamine and thyronamine, all three isoforms of the deiodinases are selenium-containing enzymes, thus dietary selenium is essential for T3 production. Edward Calvin Kendall was responsible for the isolation of thyroxine in 1915. ]]The thyroid hormones act on nearly every cell in the body. They act to increase the metabolic rate, affect protein synthesis, help regulate long bone growth and neural maturation.
The thyroid hormones are essential to development and differentiation of all cells of the human body. These hormones regulate protein and carbohydrate metabolism, numerous physiological and pathological stimuli influence thyroid hormone synthesis. Thyroid hormone leads to generation in humans. However, the function via some unknown mechanism to inhibit neuronal activity, this plays an important role in the hibernation cycles of mammals. One effect of administering the thyronamines is a drop in body temperature. Thyroid hormones are produced by the cells of the thyroid gland and are regulated by TSH made by the thyrotropes of the anterior pituitary gland. The effects of T4 in vivo are mediated via T3, T3 is 3- to 5- fold more active than T4. Thyroxine is produced by cells of the thyroid gland. It is produced as the precursor thyroglobulin, which is cleaved by enzymes to produce active T4, the steps in this process are as follows, The Na+/I− symporter transports two sodium ions across the basement membrane of the follicular cells along with an iodide ion.
This is an active transporter that utilises the concentration gradient of Na+ to move I− against its concentration gradient. I− is moved across the membrane into the colloid of the follicle
FBJ murine osteosarcoma viral oncogene homolog B, known as FOSB or FosB, is a protein that, in humans, is encoded by the FOSB gene. The FOS gene family consists of 4 members, FOS, FOSB, FOSL1 and these genes encode leucine zipper proteins that can dimerize with proteins of the JUN family, thereby forming the transcription factor complex AP-1. As such, the FOS proteins have been implicated as regulators of cell proliferation, for example, ΔFosB overexpression triggers the development of addiction-related structural neuroplasticity throughout the reward system. ΔFosB or DeltaFosB is a splice variant of FosB. ΔFosB has been implicated as a factor in the development of virtually all forms of behavioral. In the brains reward system, it is linked to changes in a number of gene products, such as CREB. In the body, ΔFosB regulates the commitment of mesenchymal cells to the adipocyte or osteoblast lineage. In the nucleus accumbens, ΔFosB functions as a molecular switch. Addiction from chronic drug use involves alterations in gene expression in the mesocorticolimbic projection.
The most important transcription factors that produce these alterations are ΔFosB, cyclic adenosine monophosphate response element binding protein, ΔFosB overexpression has been implicated in addictions to alcohol, cocaine, nicotine, phencyclidine and substituted amphetamines, among others. ΔJunD, a factor, and G9a, a histone methyltransferase. Increases in nucleus accumbens ΔJunD expression using viral vectors can reduce or, with a large increase. ΔFosB plays an important role in regulating responses to natural rewards, such as palatable food, sex. Consequently, ΔFosB is the key mechanism involved in addictions to natural rewards as well, in particular, ΔFosB inhibitors may be an effective treatment for addiction and addictive disorders. ΔFosB levels have been found to increase upon the use of cocaine, each subsequent dose of cocaine continues to increase ΔFosB levels with no ceiling of tolerance. This change can be identified rather quickly, and may be sustained weeks after the last dose of the drug, transgenic mice exhibiting inducible expression of ΔFosB primarily in the nucleus accumbens and dorsal striatum exhibit sensitized behavioural responses to cocaine.
They self-administer cocaine at lower doses than control, but have a likelihood of relapse when the drug is withheld. ΔFosB increases the expression of AMPA receptor subunit GluR2 and decreases expression of dynorphin, viral overexpression of ΔFosB in the output neurons of the nigrostriatal dopamine pathway induces levodopa-induced dyskinesias in animal models of Parkinsons disease
Second messenger system
Second messengers are intracellular signaling molecules released by the cell to trigger physiological changes such as proliferation, migration and apoptosis. Secondary messengers are therefore one of the components of intracellular signal transduction cascades. Examples of second messenger molecules include cyclic AMP, cyclic GMP, inositol trisphosphate, the cell releases second messenger molecules in response to exposure to extracellular signaling molecules—the first messengers. First messengers are extracellular factors, often hormones or neurotransmitters, such as epinephrine, growth hormone, for example, RasGTP signals link with the Mitogen Activated Protein Kinase cascade to amplify the allosteric activation of proliferative transcription factors such as Myc and CREB. Earl Wilbur Sutherland, Jr. discovered second messengers, for which he won the 1971 Nobel Prize in Physiology or Medicine, Sutherland saw that epinephrine would stimulate the liver to convert glycogen to glucose in liver cells, but epinephrine alone would not convert glycogen to glucose.
He found that epinephrine had to trigger a second messenger, cyclic AMP, the mechanisms were worked out in detail by Martin Rodbell and Alfred G. Gilman, who won the 1994 Nobel prize. These small molecules bind and activate protein kinases, ion channels and these intracellular messengers have some properties in common, They can be synthesized/released and broken down again in specific reactions by enzymes or ion channels. Some can be stored in special organelles and quickly released when needed and their production/release and destruction can be localized, enabling the cell to limit space and time of signal activity. There are several different secondary messenger systems, but they all are similar in overall mechanism, although the substances involved. In most cases, a ligand binds to a receptor protein molecule. The binding of a ligand to the causes an conformation change in the receptor. This conformation change can affect the activity of the receptor and result in the production of active second messages, in the case of G protein-coupled receptors, the conformation change exposes a binding site for a G-protein.
The G-protein is bound to the membrane of the cell. The G-protein is known as the transducer, when the G-protein binds with the receptor, it becomes able to exchange a GDP molecule on its alpha subunit for a GTP molecule. Once this exchange takes place, the subunit of the G-protein transducer breaks free from the beta and gamma subunits. The alpha subunit, now free to move along the inner membrane, the primary effector has an action, which creates a signal that can diffuse within the cell. This signal is called the second messenger, the secondary messenger may activate a secondary effector whose effects depend on the particular secondary messenger system. Calcium ions are one type of second messengers and are responsible for many important physiological functions including muscle contraction, the ions are normally bound or stored in intracellular components and can be released during signal transduction
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. Eukaryotes usually have a nucleus, but a few cell types, such as mammalian red blood cells, have no nuclei. Cell nuclei contain most of the genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones. The genes within these chromosomes are the nuclear genome and are structured in such a way to promote cell function. The nucleus maintains the integrity of genes and controls the activities of the cell by regulating gene expression—the nucleus is, because the nuclear membrane is impermeable to large molecules, nuclear pores are required to regulate nuclear transport of molecules across the envelope. The pores cross both nuclear membranes, providing a channel through which larger molecules must be transported by carrier proteins while allowing free movement of small molecules. Movement of large molecules such as proteins and RNA through the pores is required for gene expression and the maintenance of chromosomes.
The best-known of these is the nucleolus, which is involved in the assembly of ribosomes. After being produced in the nucleolus, ribosomes are exported to the cytoplasm where they translate mRNA, the nucleus was the first organelle to be discovered. What is most likely the oldest preserved drawing dates back to the early microscopist Antonie van Leeuwenhoek and he observed a lumen, the nucleus, in the red blood cells of salmon. Unlike mammalian red blood cells, those of other vertebrates still contain nuclei, the nucleus was described by Franz Bauer in 1804 and in more detail in 1831 by Scottish botanist Robert Brown in a talk at the Linnean Society of London. Brown was studying orchids under microscope when he observed an opaque area and he did not suggest a potential function. In 1838, Matthias Schleiden proposed that the plays a role in generating cells. He believed that he had observed new cells assembling around cytoblasts, Franz Meyen was a strong opponent of this view, having already described cells multiplying by division and believing that many cells would have no nuclei.
The function of the nucleus remained unclear, between 1877 and 1878, Oscar Hertwig published several studies on the fertilization of sea urchin eggs, showing that the nucleus of the sperm enters the oocyte and fuses with its nucleus. This was the first time it was suggested that an individual develops from a nucleated cell, the necessity of the sperm nucleus for fertilization was discussed for quite some time. However, Hertwig confirmed his observation in other groups, including amphibians. Eduard Strasburger produced the results for plants in 1884
AP-1 transcription factor
Activator protein 1 is a transcription factor that regulates gene expression in response to a variety of stimuli, including cytokines, growth factors and bacterial and viral infections. AP-1 controls a number of processes including differentiation, proliferation. The structure of AP-1 is a composed of proteins belonging to the c-Fos, c-Jun, ATF. AP-1 was first discovered as a TPA-activated transcription factor that bound to an element of the human metallothionein IIa promoter. The AP-1 binding site was identified as the 12-O-Tetradecanoylphorbol-13-acetate response element with the consensus sequence 5’-TGA G/C TCA-3’, the AP-1 subunit Jun was identified as a novel oncoprotein of avian sarcoma virus, and Fos-associated p39 protein was identified as the transcript of the cellular Jun gene. Fos was first isolated as the homologue of two viral v-fos oncogenes, both of which induce osteosarcoma in mice and rats. Since its discovery, AP-1 has been found to be associated with regulatory and physiological processes.
AP-1 transcription factor is assembled through the dimerization of a characteristic bZIP domain in the Fos, a typical bZIP domain consists of a “leucine zipper” region, and a “basic region”. The leucine zipper is responsible for dimerization of the Jun and Fos protein subunits, due to the amino acid sequence and the periodicity of the helices, the leucine side chains are arranged along one face of the α helix and form a hydrophobic surface that modulates dimerization. Together, this hydrophobic surface holds the two subunits together, the basic region of the bZIP domain is just upstream to the leucine zipper, and contains positively charged residues. This region interacts with DNA target sites, dimerization happens between the products of the c-jun and c-fos protooncogenes, and is required for DNA-binding. Jun proteins can form both homo and heterodimers and therefore are capable of binding to DNA by themselves, Fos proteins do not dimerize with each other and therefore can only bind to DNA when bound with Jun.
The Jun-Fos heterodimer is more stable and has higher DNA-binding activity than Jun homodimers, AP-1 transcription factor has been shown to have a hand in a wide range of cellular processes, including cell growth and apoptosis. AP-1 activity is regulated via post-translational modifications, DNA binding dimer composition. AP-1 transcription factors are associated with numerous physiological functions especially in determination of organisms’ life span. Below are some of the important functions and biological roles AP-1 transcription factors have been shown to be involved in. The AP-1 transcription factor has shown to play numerous roles in cell growth. In particular, c-Fos and c-Jun seem to be major players in these processes, c-jun has been shown to be essential for fibroblast proliferation, and levels of both AP-1 subunits have been shown to be expressed above basal levels during cell division
The term neurosteroid was coined by the French physiologist Étienne-Émile Baulieu and refers to steroids synthesized in the brain. The term neuroactive steroids was first coined in 1992 by Steven Paul, in addition to their actions on neuronal membrane receptors, some of these steroids may exert effects on gene expression via nuclear steroid hormone receptors. Neurosteroids have a range of potential clinical applications from sedation to treatment of epilepsy. Ganaxolone, an analog of the endogenous neurosteroid allopregnanolone, is under investigation for the treatment of epilepsy. Based on differences in activity and structure, neurosteroids can be categorized into different groupings. The most important neurosteroids are bolded below and these neurosteroids exert inhibitory actions on neurotransmission. Androstadienol Androstadienone Androstenol Androstenone Estratetraenol Certain other endogenous steroids, such as pregnenolone, estradiol, unlike those listed above, these neurosteroids do not modulate the GABAA or NMDA receptors, and instead affect various other cell surface receptors and non-genomic targets.
Neurosteroids are synthesized from cholesterol, which is converted into pregnenolone, neurosteroids are produced in the brain after local synthesis or by conversion of peripherally-derived adrenal steroids or gonadal steroids. They accumulate especially in myelinating glial cells, from cholesterol or steroidal precursors imported from peripheral sources, neurosteroids appear to play an important role in various sexually-dimorphic behaviors and emotional responses. Acute stress elevates the levels of inhibitory neurosteroids like allopregnanolone, and this is similar to the case of endorphins, which are released in response to stress and physical pain and counteract the negative subjective effects of such states. As such, it has suggested that one of the biological functions of these neuromodulators may be to help maintain emotional homeostasis. Elevated levels of inhibitory neurosteroids, namely allopregnanolone, can produce paradoxical effects, such as negative mood, irritability, several synthetic neurosteroids have been used as sedatives for the purpose of general anaesthesia for carrying out surgical procedures.
The best known of these are alphaxolone, hydroxydione, the first of these to be introduced was hydroxydione, which is the esterified 21-hydroxy derivative of 5β-pregnanedione. Hydroxydione proved to be a useful drug with a good safety profile. This led to the development of newer neuroactive steroids, the next drug from this family to be marketed was a mixture of alphaxolone and alphadolone, known as Althesin. This was withdrawn from use due to rare but serious toxic reactions. Neurosteroids, including ganaxolone have a spectrum of activity in animal models. They may have advantages over other GABAA receptor modulators, notably benzodiazepines, the drug continued to demonstrate efficacy in an 104-week open label extension
In the fields of molecular biology and genetics, c-Fos is a proto-oncogene that is the human homolog of the retroviral oncogene v-fos. It was first discovered in rat fibroblasts as the gene of the FBJ MSV. It is a part of a bigger Fos family of transcription factors which includes c-Fos, FosB, Fra-1 and it has been mapped to chromosome region 14q21→q31. It plays an important role in cellular functions and has been found to be overexpressed in a variety of cancers. C-fos is a 380 amino acid protein with a leucine zipper region for dimerisation and DNA-binding. Unlike Jun proteins, it cannot form homodimers, only heterodimers with c-jun, in vitro studies have shown that Jun–Fos heterodimers are more stable and have stronger DNA-binding activity than Jun–Jun homodimers. A variety of stimuli, including serum, growth factors, tumor promoters, the c-fos mRNA and protein is generally among the first to be expressed and hence referred to as an immediate early gene. It is rapidly and transiently induced, within 15 minutes of stimulation and it can cause gene repression as well as gene activation, although different domains are believed to be involved in both processes.
It can induce a loss of polarity and epithelial-mesenchymal transition, leading to invasive. The AP-1 complex has been implicated in transformation and progression of cancer, in osteosarcoma and endometrial carcinoma, c-Fos overexpression was associated with high-grade lesions and poor prognosis. Also, in a comparison between precancerous lesion of the cervix uteri and invasive cervical cancer, c-Fos expression was lower in precancerous lesions. C-Fos has identified as independent predictor of decreased survival in breast cancer. Several studies have raised the idea that c-Fos may have tumor-suppressor activity, supporting this is the observation that in ovarian carcinomas, loss of c-Fos expression correlates with disease progression. This double action could be enabled by differential protein composition of cells and their environment, for example, dimerisation partners, co-activators. It is possible that the tumor suppressing activity is due to a proapoptotic function, fas ligand and the tumour necrosis factor-related apoptosis-inducing ligand might reflect an additional apoptotic mechanism induced by c-Fos, as observed in a human T-cell leukaemia cell line.
Another possible mechanism of c-Fos involvement in tumour suppression could be the direct regulation of BRCA1, methamphetamine and other psychoactive drugs have been shown to increase c-fos production in the mesocortical pathway as well as in the mesolimbic reward pathway. Accumbal c-Fos repression by ΔFosBs AP-1 complex acts as a switch for the long-term induction of ΔFosB. An increase in production in androgen receptor-containing neurons has been observed in rats after mating
The cell membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is permeable to ions and organic molecules and controls the movement of substances in. The basic function of the membrane is to protect the cell from its surroundings. It consists of the bilayer with embedded proteins. Cell membranes can be artificially reassembled, Some authors that did not believe that there was a functional permeable boundary at the surface of the cell preferred to use the term plasmalemma to the extern region of the cell. The cell membrane surrounds the cytoplasm of living cells, physically separating the components from the extracellular environment. The cell membrane plays a role in anchoring the cytoskeleton to provide shape to the cell, bacteria, most archaea, and plants have a cell wall, which provides a mechanical support to the cell and precludes the passage of larger molecules. The cell membrane is permeable and able to regulate what enters and exits the cell.
The movement of substances across the membrane can be passive, occurring without the input of cellular energy, or active. The membrane maintains the cell potential, the cell membrane thus works as a selective filter that allows only certain things to come inside or go outside the cell. The cell employs a number of mechanisms that involve biological membranes,1. Passive osmosis and diffusion, Some substances such as carbon dioxide and oxygen, can move across the membrane by diffusion. Because the membrane acts as a barrier for certain molecules and ions, such a concentration gradient across a semipermeable membrane sets up an osmotic flow for the water. Transmembrane protein channels and transporters, such as sugars or amino acids, must enter the cell, such molecules diffuse passively through protein channels such as aquaporins in facilitated diffusion or are pumped across the membrane by transmembrane transporters. Protein channel proteins, called permeases, are quite specific and transporting only a limited food group of chemical substances.
Endocytosis, Endocytosis is the process in which cells absorb molecules by engulfing them, the plasma membrane creates a small deformation inward, called an invagination, in which the substance to be transported is captured. The deformation pinches off from the membrane on the inside of the cell, Endocytosis is a pathway for internalizing solid particles, small molecules and ions, and macromolecules. Endocytosis requires energy and is thus a form of active transport and this is the process of exocytosis