CtpB is a plasma membrane copper (I) transporting P-type ATPase of Mycobacterium tuberculosis

BACKGROUND: The intracellular concentration of heavy-metal cations, such as copper, nickel, and zinc is pivotal for the mycobacterial response to the hostile environment inside macrophages. To date, copper transport mediated by P-type ATPases across the mycobacterial plasma membrane has not been sufficiently explored. RESULTS: In this work, the ATPase activity of the putative Mycobacterium tuberculosis P1B-type ATPase CtpB was associated with copper (I) transport from mycobacterial cells. Although CtpB heterologously expressed in M. smegmatis induced tolerance to toxic concentrations of Cu2+ and a metal preference for Cu+, the disruption of ctpB in M. tuberculosis cells did not promote impaired cell growth or heavy-metal accumulation in whole mutant cells in cultures under high doses of copper. In addition, the Cu+ ATPase activity of CtpB embedded in the plasma mem-brane showed features of high affinity/slow turnover ATPases, with enzymatic parametersKM 0.19 ± 0.04 µM and Vmax 2.29 ± 0.10 nmol/mg min. In contrast, the ctpB gene transcription was activated in cells under culture conditions that mimicked the hostile intraphagosomal environment, such as hypoxia, nitrosative and oxidative stress, but not under high doses of copper. CONCLUSIONS: The overall results suggest that M. tuberculosis CtpB is associated with Cu+ transport from mycobacterial cells possibly playing a role different from copper detoxification.

Research progress in Menkes disease / 国际儿科学杂志

Menkes Disease (MD) is a multisystemic disorder of impaired copper metabolism with an X-linked recessive inheritance,which is caused by defects in ATP7A gene encoding a copper-transporting AT-Pase.It is characterized by infantile onset,peculiar curls and facial changes,mental retardation with progressive neurodegeneration,as well as hypotonia and connective tissue abnormalities.Many intermediate phenotypes have been found in recent years,the mildest form of which is occipital horn syndrome (OHS).Its clinical variants show a broad spectrum from chromosome abnormalities to single-nucleotide mutation.Early copper-histidine supplementation is still the most crucial treatment at present,and L-DOPS combination therapy may benefit some patients clinically.This article reviews the pathogenesis,clinical features and the progress of diagnosis and treatment of MD.

Change of CTR1 Expression after Round Window Niche Copper Sulfate and Cisplatin Infusion / 听力学及言语疾病杂志

Objective To study the expression of copper transport protein 1 in the inner ear of rat and the changes of CTR1 expression after those round window niche copper sulfate and cisplatin infusion .Methods 24 male wistar rats were randomly divided into 4 groups :Group I as the normal control group (nontreatment group);Group II as the round window niche cisplatin infusion group(0 .5 mg/ml);Group III as the round window niche cisplatin infusion group (1 mg/ml);group IV as the round window niche copper sulfate infusion (0 .02 mg/kg) .The CTR1 protein was detected by the immunohistochemical (IHC) otaining and Western-blot ,and the CTR1mRNA expres‐sion levels were detected by RT -PCR .Results The expression of CTR1 protein was observed in the cytoplasm and cell membrane of Corti organ cells ,spiral ganglion cells and stria vascularis in all groups .The average optical densi‐ties of CTR1 protein was a downward trend .The expression of CTR1 protein was observed in four different groups . The optical density analysis of CTR1 showed that the optical densities were 0 .532 ± 0 .031 ,0 .394 ± 0 .024 ,0 .234 ± 0 .030 and 0 .191 ± 0 .015 ,respectively .There was a downward trend ,and there were statistically differences among the groups (P<0 .05) .The CTR1 mRNA was observed in all groups .The optical density analysis of CTR1 mRNAshowed that the optical densities were 0 .508 ± 0 .035 ,0 .391 ± 0 .022 ,0 .240 ± 0 .02 and 0 .186 ± 0 .021 ,respective‐ly .It had a downward trend and were statistically differences among the groups (P<0 .05) .Conclusion The CTR1 protein was abundantly expressed in Corti organ ,spiral ganglion cells and stria vascularis of the cochlea .The round window cisplatin and copper sulfate infusion can change the expression of CTR1 proteins in inner ear .