Sarcoplasmic Reticulum Calcium-Transporting ATPases

Publication Title: 
Malaria Journal

BACKGROUND: Evaluating copy numbers of given genes in Plasmodium falciparum parasites is of major importance for laboratory-based studies or epidemiological surveys. For instance, pfmdr1 gene amplification has been associated with resistance to quinine derivatives and several genes involved in anti-oxidant defence may play an important role in resistance to antimalarial drugs, although their potential involvement has been overlooked.

Ferreira, Isabel D.
Rosário, Virgílio E. do
Cravo, Pedro V. L.
Publication Title: 
Eukaryotic Cell

Intracellular calcium controls several crucial cellular events in apicomplexan parasites, including protein secretion, motility, and invasion into and egress from host cells. The plant compound thapsigargin inhibits the sarcoplasmic-endoplasmic reticulum calcium ATPase (SERCA), resulting in elevated calcium and induction of protein secretion in Toxoplasma gondii. Artemisinins are natural products that show potent and selective activity against parasites, making them useful for the treatment of malaria.

Nagamune, Kisaburo
Beatty, Wandy L.
Sibley, L. David
Publication Title: 
British Journal of Pharmacology

BACKGROUND AND PURPOSE: Artemisinin is an antimalarial drug exerting pleiotropic effects, such as the inhibition of the transcription factor nuclear factor-kappa B and of the sarcoplasmic/endoplasmic reticulum Ca(++)-ATPase (SERCA) of P. falciparum.

Riganti, C.
Doublier, S.
Viarisio, D.
Miraglia, E.
Pescarmona, G.
Ghigo, D.
Bosia, A.
Publication Title: 
International Journal of Cancer. Journal International Du Cancer

Analogs of the malaria therapeutic, artemisinin, possess in vitro and in vivo anticancer activity. In this study, two dimeric artemisinins (NSC724910 and 735847) were studied to determine their mechanism of action. Dimers were >1,000 fold more active than monomer and treatment was associated with increased reactive oxygen species (ROS) and apoptosis induction. Dimer activity was inhibited by the antioxidant L-NAC, the iron chelator desferroxamine and exogenous hemin.

Stockwin, Luke H.
Han, Bingnan
Yu, Sherry X.
Hollingshead, Melinda G.
Elsohly, Mahmoud A.
Gul, Waseem
Slade, Desmond
Galal, Ahmed M.
Newton, Dianne L.
Bumke, Maja A.
Publication Title: 
The Journal of Biological Chemistry

The antimalarial drugs artemisinins have been described as inhibiting Ca(2+)-ATPase activity of PfATP6 (Plasmodium falciparum ATP6) after expression in Xenopus oocytes. Mutation of an amino acid residue in mammalian SERCA1 (Glu(255)) to the equivalent one predicted in PfATP6 (Leu) was reported to induce sensitivity to artemisinin in the oocyte system. However, in the present experiments, we found that artemisinin did not inhibit mammalian SERCA1a E255L either when expressed in COS cells or after purification of the mutant expressed in Saccharomyces cerevisiae.

Cardi, Delphine
Pozza, Alexandre
Arnou, Bertrand
Marchal, Estelle
Clausen, Johannes D.
Andersen, Jens Peter
Krishna, Sanjeev
Møller, Jesper V.
le Maire, Marc
Jaxel, Christine
Publication Title: 
Antimicrobial Agents and Chemotherapy

Artemisinin-based combination therapies (ACTs) are highly effective for the treatment of Plasmodium falciparum malaria, yet their sustained efficacy is threatened by the potential spread of parasite resistance. Recent studies have provided evidence that artemisinins can inhibit the function of PfATP6, the P. falciparum ortholog of the ER calcium pump SERCA, when expressed in Xenopus laevis oocytes. Inhibition was significantly reduced in an L263E variant, which introduced the mammalian residue into a putative drug-binding pocket.

Valderramos, Stephanie Gaw
Scanfeld, Daniel
Uhlemann, Anne-Catrin
Fidock, David A.
Krishna, Sanjeev
Publication Title: 
Antimicrobial Agents and Chemotherapy

Recent reports on the decline of the efficacy of artemisinin-based combination therapies (ACTs) indicate a serious threat to malaria control. The endoplasmic/sarcoplasmic reticulum Ca(2+)-ATPase ortholog of Plasmodium falciparum (PfSERCA) has been suggested to be the target of artemisinin and its derivatives. It is assumed that continuous artemisinin pressure will affect polymorphism of the PfSERCA gene (serca) if the protein is the target.

Tanabe, Kazuyuki
Zakeri, Sedigheh
Palacpac, Nirianne Marie Q.
Afsharpad, Manada
Randrianarivelojosia, Milijaona
Kaneko, Akira
Marma, Aung Swi Prue
Horii, Toshihiro
Mita, Toshihiro
Publication Title: 
The American Journal of Tropical Medicine and Hygiene

Plasmodium falciparum resistance to the primary drugs used for treatment of malaria has become the main obstacle to malaria control. Artemisinin combination therapies are the current treatment strategy, and it has been suggested that resistance to artemisinin derivatives may be related to mutations in the Plasmodium falciparum sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase ortholog of the mammalian sarco-endoplasmic reticulum Ca(2+) ATPase gene, known as the pfatp6 gene. Thus, the purpose of this study was to determine the prevalence of single-nucleotide polymorphisms (SNPs) in pfatp6.

Fernández-Martínez, Amalia
Mula, Patricia
Cravo, Pedro
Charle, Pilar
Amor, Aranzazu
Ncogo, Policarpo
Benito, Agustín
Berzosa, Pedro
Publication Title: 
American Journal of Physiology. Heart and Circulatory Physiology

Glycemic regulation improves myocardial function in diabetic patients, but finding optimal therapeutic strategies remains challenging. Recent data have shown that pharmacological inhibition of soluble epoxide hydrolase (sEH), an enzyme that decreases the endogenous levels of protective epoxyeicosatrienoic acids (EETs), improves glucose homeostasis in insulin-resistant mice. Here, we tested whether the administration of sEH inhibitors preserves cardiac myocyte structure and function in hyperglycemic rats.

Guglielmino, Kathleen
Jackson, Kaleena
Harris, Todd R.
Vu, Vincent
Dong, Hua
Dutrow, Gavin
Evans, James E.
Graham, James
Cummings, Bethany P.
Havel, Peter J.
Chiamvimonvat, Nipavan
Despa, Sanda
Hammock, Bruce D.
Despa, Florin
Publication Title: 
Zhong Xi Yi Jie He Xue Bao = Journal of Chinese Integrative Medicine

OBJECTIVE: To investigate the mechanism of Chaiqin Chengqi Decoction (CQCQD), a compound of traditional Chinese herbal medicine, acting on the pancreatic acinar cell calcium overload in rats with acute pancreatitis (AP). METHODS: A total of 30 SD rats were randomly divided into normal control group, untreated group and CQCQD group (n=10, respectively). AP was induced in rats by caerulein (5x50 mug/kg) intraperitoneal injection within 4 h.

Xue, Ping
Deng, Li-Hui
Zhang, Zhao-da
Yang, Xiao-nan
Xia, Qing
Xiang, Da-Kai
Huang, Lei
Wan, Mei-Hua
Zhang, Hai-Yan


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