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Apoptosis

Apoptosis is a fundamental biological phenomenon that is widespread in life. It plays a very important role as cell growth, development and proliferation. Now it is thought that one of the important markers for it is that: the extracellular stimuli that cause induction of apoptosis must undergo a series of intracellular signal transduction, resulting in selective DNA fracture between nucleosomes. The term was first proposed in the 1970s, referring to the gene-controlled mild death of single kinds of cells under certain physiological or pathological conditions. During the emergence and development of multi-cellular organisms, in order to maintain normal physiological function, a fraction of the cells will undergo spontaneous cell death. The kind of spontaneous cell death is regulated by a series of related intracellular regulatory molecules, and is accompanied by typical morphological changes. This phenomenon is called apoptosis.

Apoptosis refers to the process that the cell undergoes automatic end of life under certain physiological or pathological conditions via internal controlled genetic mechanisms. Instead, programmed cell death (PCD) refers to responsive death of cells to certain physiological stimuli during the biological processes of development, it requires a certain level of gene expression. Apoptosis refers to the description of series of fixed-pattern of morphological changes during the process of cell death while PCD mainly focused on the concept of function. There are differences between these two terms, but are still often confused.

Apoptosis or programmed cell death (PCD) is an active spontaneous cell death process adopted multi-cellular organism in order to regulate the body's development and maintain the homeostasis. It is controlled by the Pb gene. Currently, the spontaneous degenerative cell death phenomena have various names. The most commonly used is programmed cell death (PCD), it was originally used in the subject of embryonic development. During the differentiation process of embryonic cells, the spontaneous degenerative death of the specific parts of cells is due to that intracellular genes of this part have undergone expression according to certain program, also known as gene mandatory cell death, physiological cell death, naturally occurring cell death, cell suicide and apoptosis.

Apoptosis is characterized by series of morphological changes including concentrated nucleus, the fragmentation of chromosomal DNA into ladder fragment in nucleosome units, cells shrinking and eventually forming apoptotic body. It does not cause the dissolution of surrounding cells. Apoptosis dispersively and periodically progress in the population of cells and also depends on the supply of ATP and RNA as well as protein synthesis, belonging to active exclusion mechanisms. It can not only be observed during the physiological conditions such as ontogeny and egg withdrawal, but also can be observed in many diseases and pathological conditions such as autoimmune diseases, neurological deterioration diseases and ischemic diseases. The intracellular information transduction pathway can be roughly divided into two stages, namely the induction phase and the implementation phase.

The induction factors in the induction phase of apoptosis include endogenous and exogenous factors. Endogenous factors include the activation of the apoptosis-inducing mechanisms (such as Fas ligand and tumor necrosis factor, etc.) and inactivation of the inhibitory mechanisms (growth factors, hormones, growth factor receptors and other factors). Exogenous factors include physical factors including radiation and heat shock, chemical factors such as drugs and poisons and biological factors such as viruses and bacteria. In recent years, it has been also found that that the effects of reactive oxygen and nitric oxide in nervous system disorders, cardiovascular disease, autoimmune diseases and aging are more or less related to the apoptosis.

Recent studies have shown that the key step of apoptosis doesn’t occur at cell nuclei, but in the cytoplasm. Before the apoptotic cells were induced of morphological properties changes and DNA degradation, the mitochondrial membrane function changes, endometrial transmembrane potential will disappear and the protease activator inside the mitochondria will be released, stimulating the apoptosis associated various metabolic changes.

The biological function s of apoptosis
(1) Eliminate useless or unwanted cells; during the development process of the human brain, 95% of cells undergo cell death.
(2)Eliminate the cells that no longer function such as the tail cell death during tadpole metamorphosis; the mammalian endometrial epithelial cell death during the menstrual period.
(3) Remove the cells undergoing abnormal development. For example, during the development of the vertebrate visual system, if the neurons don’t form the correct neurons connections, they will be removed.
(4) Remove some harmful cells. For example, thymocytes will be induced of death before leaving the thymus.

Process of apoptosis
Apoptotic process can be divided into four stages:
(1) Signal transduction of apoptosis
After the binding of the intra-/extra-cellular cell apoptosis inducing factor to the targeted cellular receptor, the cells will produce complex biochemical reactions, forming apoptosis related second messenger: signaling molecules such as cAMP, Ca2 + and ceramide will form death signal.
(2) Activation of apoptotic gene
Regulatory apoptotic genes, after receiving death signal, start the onset according to predetermined program, and start the synthesis of various enzymes and apoptosis related substances.
(3) The execution of apoptosis (common pathway)
The major executors of apoptosis include two types of enzymes: endonuclease (endogenous nuclease Dnase) - the complete destruction of the cell biological command system; Caspases 3 – the complete disintegration of the cell structure.
(4) Removal of apoptotic cells
After apoptosis, cells can be decomposed by neighboring macrophages.

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Structure Chemical Name CAS MF
Pomalidomide Pomalidomide 19171-19-8 C13H11N3O4
ABT 737 ABT 737 852808-04-9 C42H45ClN6O5S2
Necrostatin-1 Necrostatin-1 4311-88-0 C13H13N3OS
Z-VAD-FMK Z-VAD-FMK 187389-52-2 C22H30FN3O7
Obatoclax mesilate Obatoclax mesilate 803712-79-0 C20H19N3O.CH4O3S
HA14-1 HA14-1 65673-63-4 C17H17BrN2O5
ABT 263 ABT 263 923564-51-6 C47H55ClF3N5O6S3
5,5'-(2,5-FURANDIYL)BIS-2-THIOPHENEMETHANOL 5,5'-(2,5-FURANDIYL)BIS-2-THIOPHENEMETHANOL 213261-59-7 C14H12O3S2
YM155 YM155 781661-94-7 C20H19BrN4O3
Pifithrin-α (PFTα) Pifithrin-α (PFTα) 63208-82-2 C16H19BrN2OS
TENOVIN-1 TENOVIN-1 380315-80-0 C20H23N3O2S
TW-37 TW-37 877877-35-5 C33H35NO6S
SALUBRINAL SALUBRINAL 405060-95-9 C21H17Cl3N4OS
PAC1 PAC1 315183-21-2 C23H28N4O2
1-(3,4-DICHLOROBENZYL)-1H-INDOLE-2,3-DIONE 1-(3,4-DICHLOROBENZYL)-1H-INDOLE-2,3-DIONE 79183-19-0 C15H9Cl2NO2
Z-DEVD-FMK Z-DEVD-FMK 210344-95-9 C30H41FN4O12
(S)-1-((S)-2-(4-amino-3-chlorobenzamido)-3,3-dimethylbutanoyl)-N-((2R,3S)-2-ethoxy-5-oxotetrahydrofuran-3-yl)pyrrolidine-2-carboxamide (S)-1-((S)-2-(4-amino-3-chlorobenzamido)-3,3-dimethylbutanoyl)-N-((2R,3S)-2-ethoxy-5-oxotetrahydrofuran-3-yl)pyrrolidine-2-carboxamide 273404-37-8 C24H33ClN4O6
ABT-199 ABT-199 1257044-40-8 C45H50ClN7O7S
Birinapant Birinapant 1260251-31-7 C42H56F2N8O6
AT-101 AT-101 866541-93-7 C32H34O10
 Nutlin 3a Nutlin 3a 675576-98-4 C30H30Cl2N4O4
4-[[4,5-Bis(4-chlorophenyl)-4,5-dihydro-2-[4-methoxy-2-(1-methylethoxy)phenyl]-1H-imidazol-1-yl]carbonyl]-2-piperazinone 4-[[4,5-Bis(4-chlorophenyl)-4,5-dihydro-2-[4-methoxy-2-(1-methylethoxy)phenyl]-1H-imidazol-1-yl]carbonyl]-2-piperazinone 890090-75-2 C30H30Cl2N4O4
Tenovin-6 Tenovin-6 1011557-82-6 C25H34N4O2S
BI-97C1 BI-97C1 1228108-65-3 C42H40N2O8
GDC-0152 GDC-0152 873652-48-3 C25H34N6O3S
RG-7388 RG-7388 1229705-06-9 C31H29Cl2F2N3O4
Pifithrin-μ Pifithrin-μ 64984-31-2 C8H7NO2S
Nutlin-3b Nutlin-3b 675576-97-3 C30H30Cl2N4O4
SAR405838 (MI-773) SAR405838 (MI-773) 1303607-60-4 C29H34Cl2FN3O3
NSC319726 NSC319726 71555-25-4 C11H14N4S
UMI-77 UMI-77 518303-20-3 C18H14BrNO5S2
7Methyl-5-(1-{[3-(trifluoroMethyl)phenyl]acetyl}-2,3-dihydro1Hindol-5-yl)7Hpyrrolo[2,3d]pyriMidin-4-aMine 7Methyl-5-(1-{[3-(trifluoroMethyl)phenyl]acetyl}-2,3-dihydro1Hindol-5-yl)7Hpyrrolo[2,3d]pyriMidin-4-aMine 1337531-36-8 C24H20F3N5O
BAM7 BAM7 331244-89-4 C21H19N5O2S
LCL-161 LCL-161 1005342-46-0 C26H33FN4O3S
GSK2656157 GSK2656157 1337532-29-2 C23H21FN6O
BV6 BV6 1001600-56-1 C70H96N10O8
Tasisulam Tasisulam 519055-62-0 C11H6BrCl2NO3S2
4-(4-Methyl-1-piperazinyl)-7-nitrobenzofurazane 3-oxide 4-(4-Methyl-1-piperazinyl)-7-nitrobenzofurazane 3-oxide 58131-57-0 C11H13N5O4
ISRIB (trans-isoMer) ISRIB (trans-isoMer) 1597403-47-8 C22H24Cl2N2O4
YH239-EE YH239-EE 1364488-67-4 C25H27Cl2N3O4
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