Insights into the Relationship of Catalytic Activity and Structure: A Comparison Study of Three Carbonic Anhydrase Mimics

2014 ◽  
Vol 46 (11) ◽  
pp. 683-700 ◽  
Author(s):  
RENHU MA ◽  
GEORGE F. SCHUETTE ◽  
LINDA J. BROADBELT
2006 ◽  
Vol 290 (5) ◽  
pp. F1009-F1015 ◽  
Author(s):  
Aihua Deng ◽  
Cynthia M. Miracle ◽  
Mark Lortie ◽  
Joseph Satriano ◽  
Francis B. Gabbai ◽  
...  

Oxygen consumed by the kidney (QO2) is primarily obligated to sodium reabsorption (TNa). The relationship of QO2 to TNa (QO2/TNa) may be altered by hormones and autacoids. To examine whether QO2/TNa depends on the mechanism of sodium reabsorption, we first evaluated the effects on QO2 and QO2/TNa of benzolamide (BNZ), a proximal diuretic that works by inhibiting membrane carbonic anhydrase. During BNZ infusion in anesthetized rats, QO2 increased by 50% despite a 25% decline in TNa. However, BNZ failed to increase QO2/TNa when given along with the adenosine A1 receptor blocker, DPCPX, which inhibits basolateral Na-bicarbonate cotransport (NBC1), or EIPA, which inhibits sodium-hydrogen exchange (NHE). Incubating freshly harvested rat proximal tubules with BNZ also caused QO2to increase by 62%, an effect that was prevented by blocking the apical NHE3 with S3226. Blocking NBC1 or NHE3 in the proximal tubule will have opposite effects on cell pH, but both maneuvers should reduce active chloride transport. In conclusion, inhibiting membrane carbonic anhydrase in the proximal tubule increases QO2 and reduces the energy efficiency of sodium reabsorption by the kidney. This is not purely due to shifting the burden of reabsorption to a more expensive site downstream from the proximal tubule. Instead, increased cost may be incurred within the proximal tubule as the result of increased active chloride transport.


2021 ◽  
Author(s):  
Chaofu Li ◽  
Li Qin ◽  
Jian Huang ◽  
Yu Zhan ◽  
Guanzhen Yu ◽  
...  

Abstract Background Cholangiocarcinoma (CCA) is a rare tumor with an aggressive behavior, early diagnosis is impossible as symptoms emerge only in advanced stages. The discovery of a promising biomarker is urgently needed. Carbonic anhydrase 2 (CA2) was found to be dysregulated in diverse cancers, however limited knowledge of CA2 in CCA development was known. Materials and methods CA2 expression was detected both in human and rat thioacetamide (TAA)-induced CCA model by RT-PCR and IHC staining. The relationship of CA2 expression with clinical outcomes was evaluated by univariate and multivariate analyses. CA2 expression changes were also detected both in vivo and in vitro by a potential CA2 inhibitor, Metformin (Met), which was used to inhibit CCA development. Results The level of CA2 expression was increased in biliary lesions with continuous administration of TAA. CA2 was overexpressed in CCA compared with normal tissue samples in rat model and human samples, and correlated significantly with disease progression. Patients with high CA2 expression had a poorer outcome than those without CA2 expression. Met alleviated TAA-induced CCA lesions, and significantly decreased CA2 expression. Colony formation assay showed Met inhibition in CCA cell abilities to form colonies and CA2 expression. CA2 expression was downregulated by Met in a dose- and time-dependent manner in vitro. Conclusions These findings indicate that CA2 is a promising predictive and prognostic factor, and might serve as a potentially novel therapeutic target for human CCA.


Carbon ◽  
2020 ◽  
Vol 158 ◽  
pp. 238-243 ◽  
Author(s):  
Naomi Levy ◽  
Oran Lori ◽  
Shmuel Gonen ◽  
Michal Mizrahi ◽  
Sharon Ruthstein ◽  
...  

Paleobiology ◽  
1980 ◽  
Vol 6 (02) ◽  
pp. 146-160 ◽  
Author(s):  
William A. Oliver

The Mesozoic-Cenozoic coral Order Scleractinia has been suggested to have originated or evolved (1) by direct descent from the Paleozoic Order Rugosa or (2) by the development of a skeleton in members of one of the anemone groups that probably have existed throughout Phanerozoic time. In spite of much work on the subject, advocates of the direct descent hypothesis have failed to find convincing evidence of this relationship. Critical points are:(1) Rugosan septal insertion is serial; Scleractinian insertion is cyclic; no intermediate stages have been demonstrated. Apparent intermediates are Scleractinia having bilateral cyclic insertion or teratological Rugosa.(2) There is convincing evidence that the skeletons of many Rugosa were calcitic and none are known to be or to have been aragonitic. In contrast, the skeletons of all living Scleractinia are aragonitic and there is evidence that fossil Scleractinia were aragonitic also. The mineralogic difference is almost certainly due to intrinsic biologic factors.(3) No early Triassic corals of either group are known. This fact is not compelling (by itself) but is important in connection with points 1 and 2, because, given direct descent, both changes took place during this only stage in the history of the two groups in which there are no known corals.


Author(s):  
D. F. Blake ◽  
L. F. Allard ◽  
D. R. Peacor

Echinodermata is a phylum of marine invertebrates which has been extant since Cambrian time (c.a. 500 m.y. before the present). Modern examples of echinoderms include sea urchins, sea stars, and sea lilies (crinoids). The endoskeletons of echinoderms are composed of plates or ossicles (Fig. 1) which are with few exceptions, porous, single crystals of high-magnesian calcite. Despite their single crystal nature, fracture surfaces do not exhibit the near-perfect {10.4} cleavage characteristic of inorganic calcite. This paradoxical mix of biogenic and inorganic features has prompted much recent work on echinoderm skeletal crystallography. Furthermore, fossil echinoderm hard parts comprise a volumetrically significant portion of some marine limestones sequences. The ultrastructural and microchemical characterization of modern skeletal material should lend insight into: 1). The nature of the biogenic processes involved, for example, the relationship of Mg heterogeneity to morphological and structural features in modern echinoderm material, and 2). The nature of the diagenetic changes undergone by their ancient, fossilized counterparts. In this study, high resolution TEM (HRTEM), high voltage TEM (HVTEM), and STEM microanalysis are used to characterize tha ultrastructural and microchemical composition of skeletal elements of the modern crinoid Neocrinus blakei.


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