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Showing posts with the label IGNOU MSCZOO MZO-001

What will happen if the Ca2+ is removed from the tight junction?

If Ca²⁺ is removed from the tight junction, it leads to breakdown of the tight junction structure, loss of cell adhesion, increased permeability, and overall disturbance of epithelial and endothelial tissue integrity. Role of Ca²⁺ in Tight Junctions Ca²⁺ plays a critical role in maintaining the structural organization of tight junctions. It helps stabilize the conformation of tight junction proteins and promotes proper adhesion between neighboring cells. Calcium is also necessary for the interaction between  tight junction proteins and the cytoskeleton.  Without calcium, the conformation of these proteins becomes unstable and the adhesion between cells weakens. What Happens When Ca²⁺ is Removed 1. Disruption of Tight Junction Structure When Ca²⁺ is removed from the extracellular environment, the tight junction proteins lose their ability to maintain proper interactions with each other. This leads to disassembly and fragmentation of the tight junction complex. 2. Loss of Cell–C...

Briefly explain how BCI-2 and MCL-1 inhibitors help in cancer treatment. Give examples (two each) of BCI-2 and MCL-1 inhibitors

Bcl-2 and Mcl-1 are  anti-apoptotic proteins  that belong to the  Bcl-2 family,  which controls the process of programmed cell death or apoptosis. In many types of cancers, these proteins are found in high levels. Because of this, the cancer cells avoid apoptosis, even when they are damaged or abnormal. This helps the cancer cells survive for a long time, grow uncontrollably and become resistant to chemotherapy or radiation. To stop this abnormal survival of cancer cells, scientists have developed special drugs called  Bcl-2 inhibitors and Mcl-1 inhibitors.  Bcl-2 and Mcl-1 inhibitors are special drugs that  block the action of these anti-apoptotic proteins.  When these proteins are blocked, the cancer cells lose their ability to avoid apoptosis. As a result, the natural process of cell death restarts. These inhibitors allow the pro-apoptotic proteins (like Bax and Bak) to become active again, which helps in triggering the death of cancer cells. B...

What are the different sub-classes of BCI2 proteins? Explain briefly based on structure and function

The Bcl-2 family of proteins is a very important group of regulatory proteins that play a major role in the intrinsic (mitochondrial) pathway of apoptosis, which is a kind of programmed cell death. These proteins mainly control the permeability of the mitochondrial outer membrane and thus regulate the release of  apoptotic factors  like  cytochrome c.  This family includes both pro-apoptotic proteins (which promote cell death) and anti-apoptotic proteins (which protect the cell from dying). Sub-classes of Bcl-2 Family Proteins These proteins are classified into different sub-classes based on the number and type of BH (Bcl-2 Homology) domains they contain, and also based on their functional role in apoptosis. There are three major sub-classes of Bcl-2 family proteins. 1. Anti-apoptotic Bcl-2 Proteins (BH1-BH4 containing proteins) These proteins inhibit apoptosis and protect cells from death. Structurally, they have  all four BH domains: BH1, BH2, BH3 and BH4. ...

What are the initiator and effector caspases? Give examples of each

Caspases are a special family of  protease enzymes  that play a very important role in apoptosis, which is also known as  programmed cell death.  These enzymes are present in an inactive form inside the cell and get activated when the cell receives a signal to die. Caspases work like a chain reaction. Some caspases get activated first and then they activate other caspases. Based on their function in the apoptosis process, caspases are mainly divided into two groups:  initiator caspases and effector caspases.  Both types work together to ensure proper and controlled death of damaged or unnecessary cells in the body. 1. Initiator Caspases: Initiator caspases are the  first enzymes  to be activated when the cell receives a death signal. These caspases act like a starting point in the apoptotic pathway. They do not break down the cell directly but instead activate other caspases (effector caspases) by cutting them at specific places. Initiator caspase...

Name any two each of fluorescent and non-fluorescent stains to measure cell death

To measure cell death in cells, scientists use special types of chemical dyes called  stains.  These stains help to identify whether the cells are alive, dead, or undergoing a specific type of death like apoptosis or necrosis. These stains can be broadly divided into two types based on their properties:  fluorescent stains  and  non-fluorescent stains. 1. Fluorescent Stains Fluorescent stains emit visible light (usually green, red and blue) when exposed to specific wavelengths of light under a fluorescence microscope. These stains are commonly used in cell biology and molecular biology labs to identify apoptotic and necrotic cells by detecting changes in their membranes or internal cell structures. Examples of fluorescent stains: 1. Propidium Iodide (PI): This dye is impermeable to live cells but easily enters dead or damaged cells due to their leaky plasma membrane. Once inside, it binds strongly to DNA and gives a  bright red fluorescence.  It is esp...

What is the principle of LDH assay for the measurement of cell death?

LDH assay is one of the most commonly used biochemical methods to measure cell membrane damage and cell death, especially during necrosis or late-stage apoptosis. LDH stands for  Lactate Dehydrogenase,  which is an intracellular enzyme found in the cytoplasm of almost all cells. Under normal conditions, LDH remains inside the cell. But when the cell membrane becomes damaged or ruptured due to stress, toxin, or cell death, LDH leaks out into the surrounding medium. The LDH assay takes advantage of this leakage to estimate the extent of cell death. Principle of the LDH Assay The principle of the LDH assay is based on the ability of LDH enzyme to catalyze a reaction that changes  lactate to pyruvate.  This reaction also results in the conversion of  NAD⁺ to NADH.  The NADH produced can then react with specific substrates to create a colored product, which can be measured using a  spectrophotometer. The overall reaction looks like this: Lactate + NAD⁺ → Py...

What are the major stages of autophagy?

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Autophagy is a highly regulated catabolic process in which cells degrade and recycle their own components like damaged organelles, misfolded proteins or excess cytoplasmic material. The word  "autophagy"  means  "self-eating"  and it is important for maintaining cellular health, especially during stress, starvation or damage. The process is controlled by  autophagy-related genes (ATG)  and it plays a crucial role in cell survival, immunity, aging and disease regulation. There are different types of autophagy, but the most studied and important one is macroautophagy, commonly referred to simply as autophagy. Major Stages of Autophagy Autophagy does not occur randomly, but in an orderly step-wise manner. There are five major stages of autophagy and each stage is controlled by specific proteins and molecular signals. 1. Initiation (Induction) In this first step, autophagy is triggered by signals such as nutrient deprivation, oxidative stress and damage. These ...

Indicate the difference between intrinsic and extrinsic apoptotic pathways

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Apoptosis  is a highly regulated process of  programmed cell death  that removes unwanted or damaged cells without causing inflammation. There are two main apoptotic pathways: the  intrinsic (mitochondrial) pathway  and  the extrinsic (death receptor) pathway.  The  intrinsic pathway  is triggered by internal stress like DNA damage, while the  extrinsic pathway  is activated by external signals such as death ligands. Even though both pathways lead to programmed cell death, they are quite different in many ways. These differences are based on various criteria such as: 1. Based on Type of Triggering Signal Intrinsic pathway  is activated by  internal cellular stress signals  such as DNA damage, oxidative stress and ER stress. These arise from within the cell itself, usually due to damage or malfunction that threatens cell survival. Extrinsic pathway  is triggered by  external signals  like binding of deat...

Differentiate between necrosis and apoptosis

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Necrosis and apoptosis are two different types of cell death. Both occur in different situations and have different effects on cells and tissues. Here are the differences  between necrosis and apoptosis bssed on different key criteria: 1. Based on Process Type and Regulation Necrosis  is an  uncontrolled,  passive and pathological type of cell death. It happens when a cell is injured suddenly due to harmful external factors like infection, mechanical trauma, or loss of blood supply. The cell does not participate in its own death. Apoptosis,  on the other hand, is a highly  regulated and controlled  physiological process. It is also called programmed cell death. Here, the cell itself activates a sequence of steps to die in a clean and safe way, especially during development or when it becomes damaged. 2. Based on Morphological Changes in Cell In necrosis,  the cell swells, organelles also swell and finally the plasma membrane breaks. This leads to ...

What are necrostatins?

In normal conditions, cells die in a controlled way through  apoptosis,  which is a peaceful and clean process that does not harm nearby tissues. But sometimes, when apoptosis is blocked or does not work properly, the body uses another backup method to kill the damaged or infected cell. This second method is called  necroptosis.  Necroptosis is a form of programmed cell death, but unlike apoptosis, it causes the cell to swell, burst and release harmful substances, which leads to inflammation and tissue damage. Necrostatins  are a group of s mall synthetic chemical molecules  that are used to block  necroptosis,  which is a type of programmed cell death. They work by stopping the activity of a key protein called  RIPK1 (Receptor Interacting Protein Kinase 1).  This protein is very important for starting the necroptosis process. If RIPK1 is blocked, then necroptosis cannot happen. The first necrostatin that was discovered is called  N...

What are BH domains? What is their importance in apoptosis?

BH domains or Bcl-2 Homology domains, are conserved amino acid sequence regions found in the members of the  Bcl-2 family of proteins,  which play an essential role in regulating apoptosis, especially in the intrinsic mitochondrial pathway. The term "BH" comes from the first discovered member of this family, Bcl-2 (B-cell lymphoma 2). These domains help in  protein-protein interactions  that either promote or prevent apoptosis, depending on the type of protein in which they are present. These BH domains are very important because they determine the pro-apoptotic or anti-apoptotic nature of the Bcl-2 family proteins. Some proteins, like Bcl-2 and Bcl-xL, help the cell survive by blocking apoptosis. Others, like Bax, Bak and Bid, help in killing the cell by starting the apoptotic process. The BH domains control these actions. Types of BH Domains There are four types of BH (Bcl-2 homology) domains and each one plays a different role in the process of apoptosis. 1. BH1 D...

Name the components of an apoptosome and a necrosome. What is the difference in the function of an apoptosome and a necrosome?

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In the cell, programmed forms of death are controlled by special protein complexes. Two important complexes among them are the  apoptosome,  which helps in the process of  apoptosis,  and the  necrosome,  which is involved in  necroptosis.  Though both are connected with cell death, their components are different and they function through separate pathways. Components of the Apoptosome: The apoptosome is a large protein complex that plays a crucial role in the intrinsic pathway of apoptosis. It forms when  mitochondrial outer membrane permeabilization (MOMP)  occurs, leading to the release of various mitochondrial factors into the cytosol. The main components of the apoptosome are: Cytochrome c:  Released from the mitochondria into the cytosol during MOMP. It plays a key role in activating the apoptosome. Apaf-1 (Apoptotic protease-activating factor 1):  A cytosolic protein that binds to cytochrome c and undergoes a conformatio...

How do pro-apoptotic proteins differ from pro-survival proteins? Give examples (two each) for both classes of proteins mentioned

In the intrinsic pathway of apoptosis, a special group of proteins called the  Bcl-2 family  plays a major role in controlling whether the cell will live or die. This family has two opposite types of proteins. First type is called  pro-apoptotic proteins,  which promote cell death. Second type is called  pro-survival proteins,  which protect the cell and stop it from dying. These pro-survival proteins are also called  anti-apoptotic proteins,  because their function is to stop apoptosis. These two groups work by controlling a key event called  mitochondrial outer membrane permeabilization (MOMP).  If pro-apoptotic proteins win, then MOMP happens and apoptosis starts. But if pro-survival proteins are stronger, then MOMP is blocked and the cell survives. Pro-apoptotic proteins These proteins promote  apoptosis  by causing damage to the outer mitochondrial membrane. They help in a critical step called mitochondrial outer membrane ...

What is mitochondrial outer membrane permeabilization (MOMP)? How is it important in the process of apoptosis?

Mitochondrial outer membrane permeabilization (MOMP)  is an essential and highly regulated step in the  intrinsic pathway of apoptosis,  which refers to the programmed and controlled death of a cell. In this process, the outer membrane of the mitochondria becomes  permeable,  meaning it develops openings or pores. As a result, certain proteins that are usually stored safely inside the mitochondrial intermembrane space get released into the  cytoplasm.  These released proteins serve as strong intracellular signals that trigger a cascade of events leading the cell towards apoptosis. Thus, MOMP acts as a critical checkpoint in deciding whether a cell will survive or enter the death pathway. MOMP does not happen suddenly or accidentally. It is highly regulated by a group of proteins known as the  Bcl-2 family.  This family includes both  pro-apoptotic proteins  and  anti-apoptotic proteins. The pro-apoptotic proteins  members ...

What are autophagosomes and autolysosomes? Indicate the major difference between the two

Inside eukaryotic cells, there is a special self-cleaning process known as  autophagy.  This process helps the cell to remove its own damaged organelles, misfolded proteins, or other unwanted cytoplasmic materials. It is especially active during stress, starvation and low energy conditions. Autophagy allows the cell to recycle these unwanted components and use them again for energy or rebuilding. During this pathway, the cell forms two important vesicle-like structures at two different stages of the process:  autophagosome  and  autolysosome.  These two structures work one after the other to complete the cleaning and recycling task. Autophagosome An autophagosome is a  double-membrane  vesicle that forms during the early stage of autophagy. It begins by surrounding the targeted material, such as damaged mitochondria and protein aggregates. This membrane keeps extending until it completely encloses the selected material, forming a sealed vesicle. A...

Explain the downstream signalling of RTKs

Receptor Tyrosine Kinases (RTKs)  are special types of transmembrane receptors that help the cell to receive and process external signals like growth factors, insulin and other peptide hormones. These signals control very important cellular processes like cell division, cell growth, metabolism, and survival. When a signal molecule binds to the RTK, it activates a cascade of events inside the cell. This entire process is known as  downstream signalling of RTKs. There are five main steps in the downstream signalling of RTKs. The signal starts from ligand binding and proceeds until intracellular kinases activate target proteins. Step 1: Ligand Binding and Receptor Dimerisation The process begins when an extracellular signalling molecule such as epidermal growth factor (EGF) or insulin binds to the extracellular domain of RTK. Once the ligand binds, it causes dimerisation of the two RTK monomers. This means two receptor molecules come together and form a dimer. This dimerisation b...

Describe the downstream signalling of GPCRs

G-protein-coupled receptors (GPCRs)  are  transmembrane receptors  that help the cell to receive signals from the external environment and pass them inside the cell. These signals can be in the form of hormones, neurotransmitters and sensory stimuli like smell or light. When a signal binds to the receptor, it activates the intracellular machinery to start a process known as  downstream signalling.  This signalling starts after the receptor is activated and ends when the final cellular response begins. There are five main steps in the downstream signalling of GPCRs, starting from ligand binding and ending with kinase activation. Step 1: Ligand Binding and GPCR Activation The first step begins when an external ligand like  epinephrine or serotonin  binds to the extracellular part of the GPCR. This binding causes a conformational change in the structure of the receptor. Because of this shape change, the cytoplasmic portion of the GPCR becomes able to inte...

How does MAPK get activated?

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Mitogen-activated protein kinases (MAPKs)  are essential enzymes that play a crucial role in regulating a wide range of cellular activities, such as cell growth, differentiation, apoptosis and responses to stress signals. The activation of MAPK occurs through a complex signaling cascade that involves multiple stages and various proteins working in a precise sequence. There are three main types of MAPK pathways: the  ERK  (extracellular signal-regulated kinase) pathway, the  JNK  (c-Jun N-terminal kinase) pathway and the  p38 MAPK  pathway. Despite differences, these pathways follow a common set of activation steps. The activation of MAPK involves a sequence of events, starting from the binding of an external signal to a cell surface receptor and ending with the regulation of gene expression in the nucleus. The process can be divided into several stages, as follows: 1. Receptor Activation: The First Step in the MAPK Cascade MAPK signaling begins when an...

Define GEFs

GEFs means  Guanine nucleotide Exchange Factors.  These are special types of regulatory proteins that are responsible for the activation of  small GTP-binding proteins (also called as GTPases).  These small GTPases, like  Ras, Rho, Rab, Ran and Arf  are molecular switches which are very important in many cellular processes like signal transduction, vesicle trafficking, cytoskeleton regulation and cell cycle control. GTP-binding proteins always exist in two forms. When they are  bound to GDP, they are inactive.  When they are  bound to GTP, they are active.  But GDP does not leave the inactive G-protein by itself because it binds tightly. Here, GEFs play an important role. GEFs help the GTPase protein to release GDP and allow a new GTP to bind. This switching from GDP to GTP turns on the GTPase. For example,  Ras protein  is a small GTPase involved in growth factor signaling. When a growth factor binds to its receptor on the mem...

Define Adaptor proteins

Adaptor proteins are  non-enzymatic intracellular proteins  that play a critical role in  cellular signaling.  They act as  linkers, bridges, or scaffolds  by connecting cell surface receptors to downstream signaling molecules, facilitating the formation of  signaling complexes.  Although adaptor proteins do not possess  enzymatic activity,  they are essential in transmitting signals by binding to specific sites on other proteins. This binding ensures the accurate transmission of signals, which is crucial for regulating various cellular functions, such as growth, differentiation, immune responses and apoptosis. In this way, adaptor proteins play a fundamental role in maintaining cellular communication and ensuring signal pathway specificity. Most adaptor proteins contain specialized structural domains, including  SH2  (Src Homology 2),  SH3  (Src Homology 3),  PTB  (Phosphotyrosine Binding) and  PDZ ...

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