Skip to main content

INTRINSIC PATHWAY OF APOPTOSIS AND ITS REGULATION BY BCL2 PROTEINS

 BCL2 PROTEINS REGULATES INTRINSIC PATHWAY OF APOPTOSIS

                                                                                 -EISHIKA DAS

In Intrinsic apoptotic pathway, mitochondrion plays a central role by releasing cytochrome C. The defining event during intrinsic apoptotic pathway Is mitochondrial outer membrane permeabilization or MOMP.
Following MOMP, cytochrome c, are released into the cytosol. Once in the cytoplasm, cytochrome c binds to adaptor protein APAF1.This interaction leads to hydrolysis of the bound dATP to dADP and a change in the conformation of APAF-1. APAF-1 assembles into a heptameric complex, the apoptosome. The APAF-1 proteins in the apoptosome then recruit initiator procaspase-9. The incorporation of procaspase-9 into the apoptosome triggers the auto-activating cleavage of procaspase-9 into caspase-9. Caspase-9, in turn, cleaves procaspase-3 to generate caspase-3, which cleaves targets that cause apoptosis of the cell.


The intrinsic apoptotic pathway is regulated by the BCL-2 family (BCL-2 stands for B-cell lymphoma/leukemia-2 gene) of proteins. This family of proteins comprise both anti-apoptotic members and pro-apoptotic members. Anti-
apoptotic members like BCL-2 itself, BCL-X and BCL-B inhibit apoptosis whereas pro-apoptotic members such as BAX, BAD, BIK promote apoptosis.
The pro-apoptotic BCL-2 proteins consist of two subfamilies - the BH123 proteins and the BH3-only proteins. The main BH123 proteins are BAX and BAK. Important members of the BH3-only proteins are BID, BIM, BIK, BAD, PUMA and NOXA. When an apoptotic stimulus triggers the intrinsic pathway, the pro-apoptotic BH123 proteins-
BAX and BAK - promotes MOMP and the release of cytochrome c and other intermembrane proteins by an unknown mechanism. BH3-only proteins, which are induced transcriptionally or post-translationally by cytotoxic stress signals, carry out their pro-apoptotic function by two mechanisms- neutralization of the anti-apoptotic BCL-2 family
proteins and direct activation of the pro-apoptotic effectors BAX and BAK. BH3-only proteins provide the crucial link between apoptotic stimuli and the intrinsic pathway of apoptosis, with different stimuli activating different BH3-only
proteins. For example, in response to DNA damage that cannot be repaired, p53 protein accumulates and activates the transcription of genes that encode the BH3-only proteins PUMA and NOXA.

Labels:

Comments

Post a Comment

please share it with your friends and students

Popular posts from this blog

Principle of MTT assay

  MTT Assay Principle : The MTT assay provides a readout of cell viability & growth that works by measuring cell metabolic activity. The yellow tetrazolium MTT (3-(4, 5-dimethyl thiazolyl-2)-2, 5-diphenyltetrazolium bromide) is reduced by the metabolically active cells, by the action of dehydrogenase enzymes, to produce reducing equivalents such as NADH and NADPH. The resulting intracellular purple formazan can be solubilized and quantified by spectrophotometric means at 570nm. MTT is sensitive to light. This assay should be performed in the dark. The MTT assay measures,  cellular metabolic activity as an indicator of cell viability, proliferation and cytotoxicity.
Post a Comment
Read more

Are Apple Seeds Poisonous? The Truth Behind Cyanide Content

  Cyanide in Apple!! 🍏 Apple 🍎seeds are often regarded as a healthy snack that is packed with numerous nutritional benefits. However, there is a concern that apple seeds contain cyanide, a toxic substance that can cause harm to the human body. In this article, we will discuss the truth behind apple seeds containing cyanide, how much cyanide is present, and whether eating apple seeds is safe or not. The truth behind apple seeds containing cyanide Apple seeds contain a small amount of cyanide, which is a poisonous chemical compound that can be harmful to the body if ingested in large amounts. The cyanide is present in the form of amygdalin, which is a glycoside that is found in the seeds of various fruits, including apples. When apple seeds are crushed or chewed, amygdalin is released and can be converted into hydrogen cyanide, a poisonous gas. How much cyanide is present in apple seeds? The amount of cyanide present in apple seeds varies depending on the variety of apple and the ...
Post a Comment
Read more

Why oxytocin and vasopressin called as 'neuro hormone'?

  Why Oxytocin and Vasopressin called as 'neuro hormone'?      -souti das                            The posterior pitutary secretes two hormone oxytocin and vasopressin(ADH).The hormones are synthesized within the cell bodies of large magnocellular neurons lying in the supraoptic and paraventricular nuclei (PVN) of the hypothalamus.                            The posterior pituitary hormones are transported in association with specific proteins, called neurophysins , along the axons of the neurons to end in those nerve terminals which lie within the posterior lobe. Prior to secretion, these hormones are stored in secretory granules either in the nerve terminals or in the varicosites called herring bodies . The hormones are secreted in response to nerve impulses originating in the supraoptic and PVN and enter the capill...
Post a Comment
Read more