The sarco/endoplasmic reticulum calcium ATPase (SERCA), which plays a key role in the maintenance of Ca2+ ion homeostasis, is an extensively studied enzyme, the inhibition of which has a considerable impact on cell life and death decision. To date, several SERCA inhibitors have been thoroughly studied and the most notable one, a derivative of the sesquiterpene lactone thapsigargin, is gradually approaching a clinical application. Meanwhile, new compounds with SERCA-inhibiting properties of natural, synthetic, or semisynthetic origin are being discovered and/or developed; some of these might also be suitable for the development of new drugs with improved performance. This review brings an up-to-date comprehensive overview of recently discovered compounds with the potential of SERCA inhibition, discusses their mechanism of action, and highlights their potential clinical applications, such as cancer treatment.
- MeSH
- Antineoplastic Agents chemistry pharmacology therapeutic use MeSH
- Gene Regulatory Networks drug effects genetics MeSH
- Enzyme Inhibitors chemistry pharmacology therapeutic use MeSH
- Humans MeSH
- Neoplasms drug therapy enzymology MeSH
- Sarcoplasmic Reticulum Calcium-Transporting ATPases antagonists & inhibitors chemistry genetics MeSH
- Protein Structure, Secondary MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Chronic kidney disease (CKD) is associated with increased concentration of intracellular calcium, which is pathological and may lead to irreversible damage of cell functions and structures. The aim of our study was to investigate the impact of 6 months vitamin D(3) supplementation (14 000 IU/week) on free cytosolic calcium concentration ([Ca(2+)](i)) and on the plasma membrane calcium ATPase (PMCA) activity of patients with CKD stage 2-3. PMCA activity of patients was also compared to that of healthy volunteers. Vitamin D(3) supplementation of CKD patients resulted in the decrease of [Ca(2+)](i) (119.79+/-5.87 nmol/l vs. 105.36+/-3.59 nmol/l, n=14, P<0.001), whereas PMCA activity of CKD patients (38.75+/-22.89 nmol P(i)/mg/h) remained unchanged after vitamin D(3) supplementation (40.96+/-17.74 nmol P(i)/mg/h, n=14). PMCA activity of early stage CKD patients before supplementation of vitamin D(3), was reduced by 34 % (42.01+/-20.64 nmol P(i)/mg/h) in comparison to healthy volunteers (63.68+/-20.32 nmol P(i)/mg/h, n=28, P<0.001). These results indicate that vitamin D(3) supplementation had a lowering effect on [Ca(2+)](i) and negligible effect on PMCA activity in CKD patients.
- MeSH
- Plasma Membrane Calcium-Transporting ATPases metabolism MeSH
- Cholecalciferol therapeutic use MeSH
- Renal Insufficiency, Chronic complications enzymology MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Vitamin D Deficiency enzymology etiology prevention & control MeSH
- Dietary Supplements MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Calcium metabolism MeSH
- Healthy Volunteers MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial MeSH
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- Adenosine Triphosphatases MeSH
- Cell Membrane MeSH
- Animal Experimentation MeSH
- Hypertrophy chemically induced physiopathology MeSH
- Isoproterenol MeSH
- Rats MeSH
- Myocardium MeSH
- Heart physiopathology MeSH
- Subcellular Fractions MeSH
- In Vitro Techniques MeSH
- Calcium metabolism MeSH
- Check Tag
- Rats MeSH
- MeSH
- Actins physiology MeSH
- Myosins physiology MeSH
- Sarcoplasmic Reticulum physiology MeSH
- Muscle Contraction MeSH
- Calcium physiology MeSH
- Publication type
- Review MeSH
