The mitochondrial electrochemical gradient is often disturbed during apoptosis and can be detected using cationic dyes such as DePsipher™ (5,5’6,6’- tetrachloro-1,1’,3,3’-tetraethylbenz-imidazolylcarbocyanine iodide) or MitoShift™ (tetramethylrhodamine ethyl ester).

Activation of caspases, or cysteinyl proteases, is a necessary event for execution of the apoptotic response.  Some of the caspases are activated early in the apoptotic process and their activation is the first step in a cascade of proteolytic cleavage of key proteins and enzymes, including other caspases and poly (ADP-ribose) polymerase (PARP). Since the substrate specificity of the caspases is high, analysis of  substrate cleavage also provides a useful biochemical marker.

The movement of some members of the Bcl-2 family from the cytoplasm to the mitochondria and the subsequent associations that occur between them and other mitochondrial membrane associated proteins are indicated to be crucial steps in apoptosis.

DNA fragmentation occurs as one of the final stages of cell death and has long been considered a hallmark of apoptosis and one of the defining biochemical events of the pathway. For detection of the DNA fragmentation associated with apoptosis by DNA laddering, the DNA  is isolated and the cleaved fragments are separated by agarose gel electrophoresis. Our Ethidium Bromide DNA Laddering kit provides the necessary reagents for detection of the DNA ladder. 

Utilizing a TUNEL-based assay, a series of kits for the in situ detection of apoptosis with colorimetric and fluorometric options was developed. The TACS® kits are tailored for the detection of DNA fragmentation associated with apoptosis in a variety of cell and tissue types and for analysis by different formats that include microscopy, flow cytometry, and 96 well plates.

Products: anti-cleaved caspase-3, anti-PARP, PARP Apoptosis Assay Kits, Bcl-2 family antibodies, DePsipher™, MitoShift™, PBR Protein, anti-PBR  

Anti-γH2AX antibody, Apoptotic DNA laddering kit, TACS•XL®, TACS® 2TdT,  VasoTACS™, FlowTACS™, TiterTACS™ 96 Well Kit, NeuroTACS™ II, TumorTACS™, CardioTACS™, DermaTACS™ 

Product Name: Celastrol
Catalog #: SIH-333-10MG
Size: 10mg
Type: Inhibitor

Datasheet: Download PDF file

Description: Proteasome inhibitor

Research Area: Apoptosis

CAS Number: 34157-83-0

Formula: C29H38O4

Molecular weight: 450.6

Source/Host: Synthetic

Purity: >98% (TLC); NMR (Conforms)

Solubility: May be dissolved in DMSO (45mg/mL) or Ethanol (30mg/mL)

Appearance: Red Powder

Safety Phrases: 

Classification: Toxic- Toxic Material Causing Immediate and Serious Toxic Effects                     
S22 - Do not breathe dust
S36/37/39 - Wear suitable protective clothing, gloves and eye/face protection
S24/25- Avoid contact with skin and eyes
Hazard Statements:                 
H301 – Toxic if swallowed                                                     
Precautionary Statements:      
P301 + P31 – If Swallowed, immediately call a POISON CENTER or doctor.   

Storage Temp: -20°C

Shipping Temp: Blue Ice or 4°C

Although not completely destroy bacterial and viral infections, penicillin has been a revolution in medicine and its introduction has saved hundreds of millions of lives in the last century. It was unique for its broad spectrum of activity. But since its introduction in medical practice so far appeared many new, exotic and constantly evolving strains of viruses and bacteria that are terrible for health capability - develop resistance to even our most powerful antibiotics.

Scientists at the lab "Lincoln" at MIT are about to end this constant race between human antibiotics and antibiotic resistance of microorganisms.
 
They created a drug that has proven effective against almost all strains of 15 of the most common viruses in the world. Rhinoviruses that cause the common cold, H1N1 flu, stomach viruses, polio virus, dengue fever and other hemorrhagic viruses, causing internal bleeding.

At present there are few drugs which are effective against specific viruses, such as HIV protease inhibitors controlling agent responsible for AIDS. Unfortunately, they are expensive and often - susceptible to viral resistance. Therefore, the researchers introduced a new approach to the problem - light, which searches and finds the infected cells, not with the virus, and with any type of viral agents. Once localized, these cells are destroyed to prevent the spread of infection.

When a virus particle infects a cell, it "distracts" cellular structures and makes them subject to one goal: to create more copies of the virus. They leave the cell, often destroying her in the process and invade new cells for the same purpose. During the process of replication, viruses establish long strands of the double-stranded RNA which is not present in human or animal organisms. The human body has a protective mechanism that is triggered by the detection of similar chains, but many viruses are able to evade detection and cause delayed immune response that usually starts too late.

To prevent this problem, Todd Rider, head of the research group introduced a new strategy against the attackers. According to it, a much more efficient than the current inducing an enhanced immune response would be, if coupled with a protein binding to the foreign RNA of another protein that induces apoptosis - programmed cell death. Similar compounds exist in nature and the team was able to combine them. Because of their natural origin, they are capable of little aid to pass through the cell membranes of all human tissues and cells. When the drug gets into the infected cell, he programmed for self-destruction, but through uninfected cells, this remains intact.

The drug has been proven non-toxic, and its few side effects do not cause serious health threats. It has already passed laboratory and experimental stage and soon became its clinical trials. If they also succeed, scientists are convinced: up to 3 years the drug could be on the market.
 
They are proud of their successes achieved so far because they believe they have found a "penicillin of the 21st century."

Researchers from the Hebrew University of Jerusalem and the Weizmann Institute of Science have developed a technique to cause apoptosis, or programmed cell death, that could lead to new approaches to treating cancer. 

Apoptosis is an essential defense mechanism against the spread of abnormal cells such as cancer. It is a complex process that occurs through networks of proteins that interact with each other. Cancer cells usually avoid this process due to mutations in the genes that encode the relevant proteins. The result is that the cancer cells survive and take over while healthy cells die.

The research, by graduate student Chen Hener-Katz at the Hebrew University, involved collaboration between Prof. Assaf Friedler of the Hebrew University's Institute of Chemistry and Prof. Atan Gross of the Weizmann Institute's Department of Biological Regulation. It was published in the Journal of Biological Chemistry under the title ''Molecular Basis of the Interaction between Proapoptotic Truncated BID (tBID) Protein and Mitochondrial Carrier Homologue 2 (MTCH2) Protein.''

The study examined the interaction between two important proteins involved in cell death: mitochondrial carrier homologue 2 (MTCH2), which was discovered in the lab of Prof. Gross, and truncated BID (tBID), which are both involved in the apoptotic process. The researchers found the regions in the two proteins that are responsible for binding to each other, a critical step in initiating apoptosis. Following their discovery, the researchers developed short synthetic protein fragments, or peptides, that mimicked the areas on the proteins that bind to each other, and by doing so inhibited this binding. In lab experiments conducted on cell cultures, this resulted in the death of cancer cells of human origin.

''These protein segments could be the basis of future anti-cancer therapies in cases where the mechanism of natural cell death is not working properly,'' said Prof. Friedler. ''We have just begun to uncover the hidden potential in the interaction between these proteins. This is an important potential target for the development of anticancer drugs that will stimulate apoptosis by interfering with its regulation. ''

Prof. Friedler is the head of the school of chemistry at the Hebrew University. His major research interests are using peptides to study protein-protein interactions in health and disease, and developing peptides as drug leads that modulate these interactions, specifically in relation to HIV and cancer. Prof. Friedler won the prestigious starting grant from the ERC (European Research Council) as well as the outstanding young scientist prize by the Israeli Chemical Society. His research was supported by a grant from the Israel Ministry of Health and by a starting grant from the European Research Council.