Publication Title: 
American Journal of Physiology. Gastrointestinal and Liver Physiology

Aquaporin 11 (AQP11) is a protein channel expressed intracellularly in multiple organs, yet its physiological function is unclear. Aqp11 knockout (KO) mice die early due to malfunction of the kidney, a result of hydropic degeneration of proximal tubule cells. Here we report the generation of liver-specific Aqp11 KO mice, allowing us to study the role of AQP11 protein in liver of mice with normal kidney function. The unchallenged liver-specific Aqp11 KO mice have normal longevity, their livers appeared normal, and the plasma biochemistries revealed only a minor defect in lipid handling.

Rojek, Aleksandra
F¸chtbauer, Ernst-Martin
F¸chtbauer, Annette
Jelen, Sabina
Malmendal, Anders
Fenton, Robert A.
Nielsen, S¯ren
Publication Title: 
Antimicrobial Agents and Chemotherapy

Endocytosis is a fundamental process of eukaryotic cells and fulfills numerous functions, most notably, that of macromolecular nutrient uptake. Malaria parasites invade red blood cells and during their intracellular development endocytose large amounts of host cytoplasm for digestion in a specialized lysosomal compartment, the food vacuole. In the present study we have examined the effects of artemisinin and the quinoline drugs chloroquine and mefloquine on endocytosis in Plasmodium falciparum.

Hoppe, Heinrich C.
van Schalkwyk, Donelly A.
Wiehart, Ursula I. M.
Meredith, Sandra A.
Egan, Joanne
Weber, Brandon W.
Publication Title: 
The EMBO journal

The P-glycoprotein homolog of the human malaria parasite Plasmodium falciparum (Pgh-1) has been implicated in decreased susceptibility to several antimalarial drugs, including quinine, mefloquine and artemisinin. Pgh-1 mainly resides within the parasite's food vacuolar membrane. Here, we describe a surrogate assay for Pgh-1 function based on the subcellular distribution of Fluo-4 acetoxymethylester and its free fluorochrome. We identified two distinct Fluo-4 staining phenotypes: preferential staining of the food vacuole versus a more diffuse staining of the entire parasite.

Rohrbach, Petra
Sanchez, Cecilia P.
Hayton, Karen
Friedrich, Oliver
Patel, Jigar
Sidhu, Amar Bir Singh
Ferdig, Michael T.
Fidock, David A.
Lanzer, Michael
Publication Title: 
Antimicrobial Agents and Chemotherapy

Artermisinin and its derivatives are now the mainstays of antimalarial treatment; however, their mechanism of action is only poorly understood. We report on the synthesis of a novel series of epoxy-endoperoxides that can be prepared in high yields from simple starting materials. Endoperoxides that are disubstituted with alkyl or benzyl side chains show efficient inhibition of the growth of both chloroquine-sensitive and -resistant strains of Plasmodium falciparum.

del Pilar Crespo, Maria
Avery, Thomas D.
Hanssen, Eric
Fox, Emma
Robinson, Tony V.
Valente, Peter
Taylor, Dennis K.
Tilley, Leann
Publication Title: 
Cancer Letters

Ginsenosides are the main bioactive components in American ginseng, a commonly used herb. In this study, we showed that the ginsenoside Rh2 exhibited significantly more potent cell death activity than the ginsenoside Rg3 in HCT116 and SW480 colorectal cancer cells. Cell death induced by Rh2 is mediated in part by the caspase-dependent apoptosis and in part by the caspase-independent paraptosis, a type of cell death that is characterized by the accumulation of cytoplasmic vacuoles.

Li, Binghui
Zhao, Jiong
Wang, Chong-Zhi
Searle, Jennifer
He, Tong-Chuan
Yuan, Chun-Su
Du, Wei
Publication Title: 
BMC complementary and alternative medicine

BACKGROUND: Protopanaxadiol (PPD) is a triterpenoid that can be prepared from steamed ginseng. PPD possesses anticancer potential via caspase-dependent apoptosis. Whether paraptosis, a type of the caspase-independent cell death, is also induced by PPD has not been evaluated. METHODS: Cell death, the cell cycle and intracellular reactive oxygen species (ROS) were analyzed by flow cytometry after staining with annexin V/PI, PI/RNase or H2DCFDA. We observed morphological changes by crystal violet staining assay. Mitochondrial swelling was measured by ultraviolet-visible spectrophotometry.

Wang, Chong-Zhi
Li, Binghui
Wen, Xiao-Dong
Zhang, Zhiyu
Yu, Chunhao
Calway, Tyler D.
He, Tong-Chuan
Du, Wei
Yuan, Chun-Su
Publication Title: 

While autophagy is believed to be beneficial for life-span extension, it is controversial which forms or aspects of autophagy are responsible for this effect. We addressed this topic by analyzing the life span of yeast autophagy mutants under caloric restriction, a longevity manipulation. Surprisingly, we discovered that the majority of proteins involved in macroautophagy and several forms of microautophagy were dispensable for life-span extension.

Tang, Fusheng
Watkins, Joseph W.
Bermudez, Maria
Gray, Russell
Gaban, Adam
Portie, Ken
Grace, Stephen
Kleve, Maurice
Craciun, Gheorghe
Publication Title: 
Oncology Reports

Ophiopogonin B (OP-B) is a bioactive component of Radix Ophiopogon Japonicus, which is often used in Chinese traditional medicine to treat pulmonary disease. However, whether or not OP-B has any potential antitumor activity has not been reported. Here, we show that the non-small cell lung cancer (NSCLC) cell lines NCI-H157 and NCI-H460 treated with OP-B grow more slowly and accumulate vacuoles in their cytoplasm compared to untreated control cells. Flow cytometric analysis showed that the cells were arrested in G0/G1 phase.

Chen, Meijuan
Du, Yuhong
Qui, Min
Wang, Mingyan
Chen, Kejun
Huang, Zhenzhou
Jiang, Miao
Xiong, Fei
Chen, Jianping
Zhou, Jing
Jiang, Fengrong
Yin, Lian
Tang, Yuping
Ye, Lihong
Zhan, Zhen
Duan, Jin-Αo
Fu, Hai-Αn
Zhang, Xu
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