Target type: biologicalprocess
Any process that activates or increases the frequency, rate or extent of glomerular visceral epithelial cell apoptotic process. [GO_REF:0000058, GOC:TermGenie, PMID:23692924]
Positive regulation of podocyte apoptotic process involves a complex interplay of signaling pathways that ultimately lead to the programmed death of podocytes, specialized cells in the kidney that form the filtration barrier. This process is tightly regulated and can be triggered by various stimuli, including:
- **Mechanical stress:** High blood pressure or glomerular hyperfiltration can damage the podocyte cytoskeleton and trigger apoptosis.
- **Immune dysregulation:** Autoantibodies against podocyte antigens can initiate apoptosis, leading to immune-mediated glomerular diseases.
- **Metabolic stress:** Conditions such as diabetes and hyperglycemia can induce oxidative stress and inflammation in podocytes, contributing to their demise.
The following pathways play key roles in positive regulation of podocyte apoptosis:
- **Intrinsic pathway:** This pathway is activated by intracellular stress signals, such as DNA damage or protein misfolding. Activation of the Bcl-2 family proteins, including Bax and Bak, leads to mitochondrial membrane permeabilization and release of cytochrome c. This triggers the formation of the apoptosome, which activates caspases, ultimately leading to apoptotic cell death.
- **Extrinsic pathway:** This pathway is initiated by extracellular signals, such as death receptor ligands (e.g., TNF-α, Fas ligand). Binding of these ligands to their respective death receptors activates caspase-8, which can either directly activate executioner caspases or activate the intrinsic pathway via Bid cleavage.
- **Growth factor withdrawal:** Podocytes require specific growth factors, such as VEGF and PDGF, for survival. Withdrawal of these factors can trigger apoptosis through the activation of the p53 pathway, leading to cell cycle arrest and eventually death.
- **Oxidative stress:** Reactive oxygen species (ROS) produced by mitochondrial dysfunction or other stimuli can damage podocyte DNA and proteins, triggering apoptosis via the intrinsic pathway.
- **Inflammation:** Inflammatory mediators, such as TNF-α and IL-1β, can activate pro-apoptotic signaling pathways and promote podocyte apoptosis.
The loss of podocytes due to apoptosis contributes to glomerular scarring and ultimately leads to progressive kidney disease. Therefore, understanding the mechanisms underlying positive regulation of podocyte apoptosis is crucial for developing therapeutic strategies aimed at preventing podocyte loss and protecting kidney function.'
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Protein | Definition | Taxonomy |
---|---|---|
Phospholipase A2 | A phospholipase A2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P04054] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
4-bromophenacyl bromide | 4-bromophenacyl bromide: phospholipidase A(2) inhibitor; structure | ||
oleanolic acid | hydroxy monocarboxylic acid; pentacyclic triterpenoid | plant metabolite | |
3-octylthio-1,1,1-trifluoro-2-propanone | 3-octylthio-1,1,1-trifluoro-2-propanone: a pesticide synergist; inhibits juvenile hormone esterase | ||
varespladib | aromatic ether; benzenes; dicarboxylic acid monoamide; indoles; monocarboxylic acid; primary carboxamide | anti-inflammatory drug; antidote; EC 3.1.1.4 (phospholipase A2) inhibitor | |
cholic acid | cholic acid : A bile acid that is 5beta-cholan-24-oic acid bearing three alpha-hydroxy substituents at position 3, 7 and 12. Cholic Acid: A major primary bile acid produced in the liver and usually conjugated with glycine or taurine. It facilitates fat absorption and cholesterol excretion. | 12alpha-hydroxy steroid; 3alpha-hydroxy steroid; 7alpha-hydroxy steroid; bile acid; C24-steroid; trihydroxy-5beta-cholanic acid | human metabolite; mouse metabolite |
curcumin | curcumin : A beta-diketone that is methane in which two of the hydrogens are substituted by feruloyl groups. A natural dyestuff found in the root of Curcuma longa. Curcumin: A yellow-orange dye obtained from tumeric, the powdered root of CURCUMA longa. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes. | aromatic ether; beta-diketone; diarylheptanoid; enone; polyphenol | anti-inflammatory agent; antifungal agent; antineoplastic agent; biological pigment; contraceptive drug; dye; EC 1.1.1.205 (IMP dehydrogenase) inhibitor; EC 1.1.1.21 (aldehyde reductase) inhibitor; EC 1.1.1.25 (shikimate dehydrogenase) inhibitor; EC 1.6.5.2 [NAD(P)H dehydrogenase (quinone)] inhibitor; EC 1.8.1.9 (thioredoxin reductase) inhibitor; EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor; EC 3.5.1.98 (histone deacetylase) inhibitor; flavouring agent; food colouring; geroprotector; hepatoprotective agent; immunomodulator; iron chelator; ligand; lipoxygenase inhibitor; metabolite; neuroprotective agent; nutraceutical; radical scavenger |
quercetin | 7-hydroxyflavonol; pentahydroxyflavone | antibacterial agent; antineoplastic agent; antioxidant; Aurora kinase inhibitor; chelator; EC 1.10.99.2 [ribosyldihydronicotinamide dehydrogenase (quinone)] inhibitor; geroprotector; phytoestrogen; plant metabolite; protein kinase inhibitor; radical scavenger | |
4-amylcinnamoylanthranilic acid | 4-amylcinnamoylanthranilic acid: phospholipase A2 inhibitor N-(p-amylcinnamoyl)anthranilic acid : An amidobenzoic acid that is anthranilic acid in which one of the anilino hydrogens is replaced by a 4-pentylcinnamoyl group. It is a transient receptor potential (TRP) channel blocker and phospholipase A2 (PLA2) inhibitor. | amidobenzoic acid; cinnamamides; secondary carboxamide | EC 3.1.1.4 (phospholipase A2) inhibitor; TRP channel blocker |
3-(4-octadecyl)benzoylacrylic acid | |||
manoalide | manoalide : A sesterterpenoid isolated from the marine sponge Luffariella variabilis and which has been shown to exhibit inhibitory activity towards phospholipase A2. manoalide: phospholipase A2 inhibitor; sesterterpene from marine sponge L. variabilis; structure given in first source | butenolide; lactol; sesterterpenoid | EC 3.1.1.4 (phospholipase A2) inhibitor; EC 5.99.1.2 (DNA topoisomerase) inhibitor; EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor; metabolite |
manoalogue | manoalogue: synthetic analog of manoalide; phospholipase A2 antagonist; structure given in first source | ||
ursodoxicoltaurine | tauroursodeoxycholate : An organosulfonate oxoanion that is the conjugate base of tauroursodeoxycholic acid arising from deprotonation of the sulfonate OH group; major species at pH 7.3. tauroursodeoxycholic acid : A bile acid taurine conjugate derived from ursoodeoxycholic acid. | bile acid taurine conjugate | anti-inflammatory agent; apoptosis inhibitor; bone density conservation agent; cardioprotective agent; human metabolite; neuroprotective agent |
indoxam | indoxam: structure in first source |