Phosphagen energy-buffering systems play an essential role in regulating the cellular energy homeostasis in periods of high-energy demand or energy supply fluctuations. Here we describe the phosphoarginine/arginine kinase system of the kinetoplastid parasite Trypanosoma brucei, consisting of three highly similar arginine kinase isoforms (TbAK1-3). Immunofluorescence microscopy using myc-tagged protein versions revealed that each isoform is located in a specific subcellular compartment: TbAK1 is exclusively found in the flagellum, TbAK2 in the glycosome, and TbAK3 in the cytosol of T. brucei. The flagellar location of TbAK1 is dependent on a 22 amino acid long N-terminal sequence, which is sufficient for targeting a GFP-fusion protein to the trypanosome flagellum. The glycosomal location of TbAK2 is in agreement with the presence of a conserved peroxisomal targeting signal, the C-terminal tripeptide ‘SNL’. TbAK3 lacks any apparent targeting sequences and is accordingly located in the cytosol of the parasite. Northern blot analysis indicated that each TbAK isoform is differentially expressed in bloodstream and procyclic forms of T. brucei, while the total cellular arginine kinase activity was 3-fold higher in bloodstream form trypanosomes. These results suggest a substantial change in the temporal and spatial energy requirements during parasite differentiation. Increased arginine kinase activity improved growth of procyclic form T. brucei during oxidative challenges with hydrogen peroxide. Elimination of the total cellular arginine kinase activity by RNA interference significantly decreased growth (>90%) of procyclic form T. brucei under standard culture conditions and was lethal for this life cycle stage in the presence of hydrogen peroxide. The putative physiological roles of the different TbAK isoforms in T. brucei are further discussed.
Objectives: This study aimed to identify the prevalences of and risk factors associated with the development of gallbladder stones and polyps in a large Chinese population. Methods: Prevalences of and risk factors for biliary stones and gallbladder polyps were retrospectively investigated among subjects who underwent a general check‐up at the Health Screening Centres of Peking Union Medical College Hospital and Beijing Charity Hospital between January 2007 and June 2010. Results: A total of 60 064 people were enrolled in the study. Overall prevalences of biliary stones and gallbladder polyps were 4.2% (n= 2527) and 6.9% (n= 4119), respectively. Risk factors associated with increased odds ratios (ORs) for the development of biliary stones were female gender (OR = 1.51), age ≥50 years (OR = 2.09), history of hypertension (OR = 1.37), thickened gallbladder wall (cholecystitis) (OR = 1.98), fasting blood glucose ≥6.10 mmol/l (OR = 1.27), body mass index ≥25 kg/m2 (OR = 1.25), systolic blood pressure ≥140 mmHg (OR = 1.31) and diastolic blood pressure ≥90 mmHg (OR = 1.44). Factors associated with gallbladder polyps were female gender (OR = 0.66), thickened gallbladder wall (OR = 2.09), negativity for hepatitis B surface antigen (HBsAg) and positivity for hepatitis B core antibody (anti‐HBc) (OR = 2.61), and positivity for both HBsAg and anti‐HBc (OR = 3.21). Conclusions: Prevalences of biliary stones and gallbladder polyps among Chinese people are similar to those reported for other populations. Biliary stones appear to be associated with female gender, age, obesity, blood glucose, blood pressure and cholecystitis. Male gender, hepatitis B virus infection and cholecystitis were strong risk factors for the formation of gallbladder polyps.
Background:TbMCP5 was predicted to function as a mitochondrial ADP/ATP carrier. Results: TbMCP5 functionally complemented ANC-deficient S. cerevisae, has biochemical properties comparable with those of ScAnc2p, and is essential for mitochondrial ADP/ATP exchange in T. brucei. Conclusion: TbMCP5 is a conserved and essential mitochondrial ADP/ATP carrier in T. brucei. Significance: TbMCP5 is the first functionally characterized mitochondrial ADP/ATP carrier from a kinetoplastid parasite.
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