human embryonic kidney
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2022 ◽  
Vol 17 (1) ◽  
pp. 1934578X2110689
Author(s):  
Ari S. Nugraha ◽  
Yoshinta D. Purnomo ◽  
Antonius N. Widhi Pratama ◽  
Bawon Triatmoko ◽  
Rudi Hendra ◽  
...  

Malaria is a neglected tropical disease that still demands serious efforts to tackle successfully, including the need for new antimalarial lead compounds to combat drug-resistant Plasmodium. Intensive phytochemical and pharmacological investigation into the Indonesian medicinal plants Swietenia mahagoni and Pluchea indica successfully revealed 5 constituents. Antimalarial bioassays indicated 34,5-tri- O-caffeoylquinic acid (4) to be the most active against Plasmodium falciparum 3D7 and Dd2 strains with IC50 values of 8.2 and 8.8 µM, respectively. No cytotoxicity was observed against Human Embryonic Kidney cells at a concentration of 40 µM.


2021 ◽  
Vol 23 (1) ◽  
pp. 117
Author(s):  
Jowita Nowakowska-Gołacka ◽  
Justyna Czapiewska ◽  
Hanna Sominka ◽  
Natalia Sowa-Rogozińska ◽  
Monika Słomińska-Wojewódzka

Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like protein 1 (EDEM1) is a quality control factor directly involved in the endoplasmic reticulum-associated degradation (ERAD) process. It recognizes terminally misfolded proteins and directs them to retrotranslocation which is followed by proteasomal degradation in the cytosol. The amyloid-β precursor protein (APP) is synthesized and N-glycosylated in the ER and transported to the Golgi for maturation before being delivered to the cell surface. The amyloidogenic cleavage pathway of APP leads to production of amyloid-β (Aβ), deposited in the brains of Alzheimer’s disease (AD) patients. Here, using biochemical methods applied to human embryonic kidney, HEK293, and SH-SY5Y neuroblastoma cells, we show that EDEM1 is an important regulatory factor involved in APP metabolism. We find that APP cellular levels are significantly reduced after EDEM1 overproduction and are increased in cells with downregulated EDEM1. We also report on EDEM1-dependent transport of APP from the ER to the cytosol that leads to proteasomal degradation of APP. EDEM1 directly interacts with APP. Furthermore, overproduction of EDEM1 results in decreased Aβ40 and Aβ42 secretion. These findings indicate that EDEM1 is a novel regulator of APP metabolism through ERAD.


2021 ◽  
pp. 101549
Author(s):  
David A. Hanna ◽  
Courtney M. Moore ◽  
Liu Liu ◽  
Xiaojing Yuan ◽  
Iramofu M. Dominic ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Riezki Amalia ◽  
Diah Lia Aulifa ◽  
Dichy Nuryadin Zain ◽  
Anisa Pebiansyah ◽  
Jutti Levita

Ethnopharmacological Relevance. In Indonesia, Angelica keiskei Koidzumi (ashitaba or Japanese celery) has been traditionally used to maintain health and to achieve longevity. Previously, the chlorophyll-rich extract of A. keiskei planted in Korea exhibited a strong antioxidant activity. The objective of the present study was to investigate the cytotoxicity and nephroprotective activity of the ethanol extract of A. keiskei Koidzumi on the N-acetyl-p-benzoquinone imine (NAPQI) induced human embryonic kidney (HEK293) cell line. Materials and Methods. A. keiskei Koidzumi plant was collected from Mount Rinjani, Lombok, Indonesia, and was identified at the School of Biology Sciences and Technology, Bandung Institute of Technology, Indonesia. Extraction of the stems (ASE) and leaves (ALE) was performed by employing ethanol 70% for 3 × 24 h at 26°C. The cytotoxicity study of the extracts was assessed using the water-soluble tetrazolium salt-8 (WST-8) reagent on the HEK293 cell line, while the nephroprotective activity assay was determined on the NAPQI-induced HEK293 cell line. Results. The WST-8 assay showed that the cytotoxicity IC50 of ASE = 2322 μg/mL and IC50 of ALE = 2283 μg/mL. The nephroprotective activity assay revealed that ASE possesses nephroprotective activity against the NAPQI-induced HEK293 cell line at 1161 μg/mL, while ALE does not show the nephroprotective activity. Conclusion. Taken together, lower concentrations of ASE and ALE (<2000 μg/mL) are not toxic to the HEK293 cell line, and only ASE indicates the activity to protect the HEK293 cell line against NAPQI damage. This Japanese celery could be further explored for its potential as a plant-based nephroprotective drug.


Life ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1134
Author(s):  
Chun Chen ◽  
Jai-Sing Yang ◽  
Chi-Cheng Lu ◽  
Yu-Tse Wu ◽  
Fu-An Chen

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat inflammation and pain and even to prevent the progression of cardiovascular disease. They have become widely used because of their effectiveness, especially among athletes performing high-intensity training. Indomethacin is used for pain management in sports medicine and is highly effective and versatile. However, several clinical studies have reported that indomethacin induces acute renal damage. In the present study, we determined that indomethacin reduced human embryonic kidney 293 (HEK293) cell viability in a concentration-dependent manner by triggering apoptosis. In addition, we demonstrated the effect of quercetin on indomethacin-treated HEK293 cells by inactivating the caspase-3 and caspase-9 signals. Furthermore, quercetin reduced ROS production and increased mitochondrial membrane potential (ΔΨm) in indomethacin-treated HEK293 cells. Our results indicate that quercetin can interrupt the activated caspase and mitochondrial pathway induced by indomethacin in HEK293 cells and affect apoptotic mRNA expression. Quercetin can protect against indomethacin-induced HEK293 cell apoptosis by regulating abnormal ΔΨm and apoptotic mRNA expression.


2021 ◽  
Vol 118 (37) ◽  
pp. e2108094118
Author(s):  
Zhihui Fong ◽  
Caoimhín S. Griffin ◽  
Roddy J. Large ◽  
Mark A. Hollywood ◽  
Keith D. Thornbury ◽  
...  

P2X1 receptors are adenosine triphosphate (ATP)-gated cation channels that are functionally important for male fertility, bladder contraction, and platelet aggregation. The activity of P2X1 receptors is modulated by lipids and intracellular messengers such as cAMP, which can stimulate protein kinase A (PKA). Exchange protein activated by cAMP (EPAC) is another cAMP effector; however, its effect on P2X1 receptors has not yet been determined. Here, we demonstrate that P2X1 currents, recorded from human embryonic kidney (HEK) cells transiently transfected with P2X1 cDNA, were inhibited by the highly selective EPAC activator 007-AM. In contrast, EPAC activation enhanced P2X2 current amplitude. The PKA activator 6-MB-cAMP did not affect P2X1 currents, but inhibited P2X2 currents. The inhibitory effects of EPAC on P2X1 were prevented by triple mutation of residues 21 to 23 on the amino terminus of P2X1 subunits to the equivalent amino acids on P2X2 receptors. Double mutation of residues 21 and 22 and single mutation of residue 23 also protected P2X1 receptors from inhibition by EPAC activation. Finally, the inhibitory effects of EPAC on P2X1 were also prevented by NSC23766, an inhibitor of Rac1, a member of the Rho family of small GTPases. These data suggest that EPAC is an important regulator of P2X1 and P2X2 receptors.


2021 ◽  
Vol 8 (03) ◽  
pp. e114-e121
Author(s):  
Qian Yang ◽  
Yinqing Li ◽  
Xizi Liu ◽  
Shiyi Han ◽  
Siyang Fan

AbstractThe rhizome of Alisma orientale (sam.) Juz. is used in clinics for eliminating dampness, reducing edema, and promoting diuresis. This study aimed to elucidate the compounds and investigate their nuclear factor-kappa inhibitory activities in human embryonic kidney 293 cells. A new triterpene, alismaketone B (1); a new natural nortriterpene, noralisolic acid A (2); and 13 known protostane-type triterpenes were isolated from the rhizome of A. orientale. The new structures and their absolute configurations were established using HRESIMS, NMR, and electronic circular dichroism experiments. All isolated compounds were evaluated for their inhibitory activity on NF-κB. The compounds 8, 9, 10, and 14 showed moderate NF-κB inhibitory activities with their IC50 values being 64.7, 32.3, 47.3, and 37.3 μM, respectively.


2021 ◽  
Vol 8 (5) ◽  
pp. e1056
Author(s):  
Julia Grüner ◽  
Helena Stengel ◽  
Christian Werner ◽  
Luise Appeltshauser ◽  
Claudia Sommer ◽  
...  

Background and ObjectivesAs autoantibodies to contactin-1 from patients with chronic inflammatory demyelinating polyradiculoneuropathy not only bind to the paranodes where they are supposed to cause conduction failure but also bind to other neuronal cell types, we aimed to investigate the effect of anti–contactin-1 autoantibodies on contactin-1 surface expression in cerebellar granule neurons, dorsal root ganglion neurons, and contactin-1–transfected human embryonic kidney 293 cells.MethodsImmunocytochemistry including structured illumination microscopy and immunoblotting was used to determine expression levels of contactin-1 and/or sodium channels after long-term exposure to autoantibodies from 3 seropositive patients. For functional analysis of sodium channels, whole-cell recordings of sodium currents were performed on dorsal root ganglion neurons incubated with anti–contactin-1 autoantibodies.ResultsWe found a reduction in contactin-1 expression levels on dorsal root ganglion neurons, cerebellar granule neurons, and contactin-1–transfected human embryonic kidney 293 cells and decreased dorsal root ganglion sodium currents after long-term exposure to anti–contactin-1 autoantibodies. Sodium channel density did not decrease.DiscussionOur results demonstrate a direct effect of anti–contactin-1 autoantibodies on the surface expression of contactin-1 and sodium currents in dorsal root ganglion neurons. This may be the pathophysiologic correlate of sensory ataxia reported in these patients.


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