Abnormal acid phosphatases in neuronal ceroid‐lipofuscinoses

Khan, Korsa; Brooks, Susan Sklower; Pullarkat, Raju K.

doi:10.1002/ajmg.1320570234

Cited by 8 publications

(4 citation statements)

References 21 publications

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“…Fluorescent detection of enzyme activities on polyacrylamide gels has previously been used for phosphatases (with 4‐methyl umbelliferyl phosphate; Khan et al . 1995) and N‐acetyl glucosaminidase (Chen et al .…”

Section: Resultsmentioning

confidence: 99%

Development of a simple and sensitive fluorimetric method for isolation of coumaphos-hydrolysing bacteria

Harcourt

Horne

Sutherland

et al. 2002

Lett Appl Microbiol

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Aims: To develop a simple, rapid and sensitive fluorimetric assay to detect, isolate and characterize a soil bacterium capable of degrading the organophosphorus pesticide, coumaphos. Methods and Results: A high throughput microtitre plate-based method was used to quantify coumaphos hydrolysis by the bacterium. The fluorescent hydrolysis product of coumaphos, chlorferon, was detected at levels as low as 10 nmol l )1 . Incorporation of coumaphos into agar plates allowed the rapid detection of coumaphos-hydrolysing bacteria when exposed to an excitation wavelength of approximately 340 nm. The coumaphos-hydrolysing enzyme could be visualized when bacterial cell extracts were separated on SDS-PAGE, incubated with coumaphos and exposed to an excitation source as above. Conclusions:This method is 100-fold more sensitive than the currently used spectrophotometric method for coumaphos. Significance and Impact of the Study: This is a unique and versatile tool to screen for bacteria possessing phosphotriesterase activity.

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Section: Resultsmentioning

confidence: 99%

Development of a simple and sensitive fluorimetric method for isolation of coumaphos-hydrolysing bacteria

Harcourt

Horne

Sutherland

et al. 2002

Lett Appl Microbiol

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“…The level of LAP/ ACP2 protein may be further affected, in a cell-dependent manner, by reduced degradation rates. LAP/Acp2 expression in Cln3-deficient mouse brain In human brain material obtained at autopsy from JNCL patients of different ages increased activities of acid phosphatase and other lysosomal enzymes were reported (Khan et al 1995;Sleat et al 1998). In contrast, in the brain of P week 9 Cln3)/) mice only LAP/ACP2 activity was increased whereas all other lysosomal enzymes examined were not or only moderately altered.…”

Section: Discussionmentioning

confidence: 98%

“…In human brain material obtained at autopsy from JNCL patients of different ages increased activities of acid phosphatase and other lysosomal enzymes were reported (Khan et al. 1995; Sleat et al.…”

Section: Discussionmentioning

confidence: 99%

Increased expression of lysosomal acid phosphatase in CLN3‐defective cells and mouse brain tissue

Pohl

Mitchison

Kohlschütter

et al. 2007

Journal of Neurochemistry

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Juvenile neuronal ceroid lipofuscinosis (Batten disease) is a neurodegenerative disorder caused by defective function of the lysosomal membrane glycoprotein CLN3. The activity of the lysosomal acid phosphatase (LAP/ACP2) was found to be significantly increased in the cerebellum and brain stem of Cln3-targeted mice during the early stages of postnatal life. Histochemical localization studies revealed an increased LAP/ ACP2 staining intensity in neurons of the cerebral cortex of 48-week-old Cln3-targeted mice as compared with controls. Additionally, the expression of another lysosomal membrane protein LAMP-2 was increased in all brain areas. Knockdown of CLN3 expression in HeLa cells by RNA interference also resulted in increased LAP/ACP2 and LAMP-2 expression. The juvenile form of neuronal ceroid lipofuscinosis (JNCL, Batten disease) is a recessively inherited neurodegenerative disease of childhood which is characterized by initial gliosis and astrocytosis followed by the progressive loss of neurons in the cortex, hippocampus, cerebellum, and the retina . Clinical features include visual loss, mental and motor retardation, epilepsy, and premature death. JNCL belongs to a group of neurodegenerative diseases with defects in ten different genes encoding both soluble and polytopic membrane proteins located in either late endosomes/lysosomes or the endoplasmic reticulum The function of CLN3 is unknown and several processes have been proposed to involve the CLN3 protein such as import of arginine into lysosomes, maturation of autophagic vacuoles, vesicular trafficking, modulation of ceramide synthesis, and apoptosis (Persaud-Sawin et al. 2002, 2004Kim et al. 2003;Luiro et al. 2004;Cao et al. 2006). The role of CLN3 in lysosomal pH homeostasis has been a matter of debate depending on the cell type and model organism being studied reporting either an increase (Pearce Received April 5, 2007; Revised July 27, 2007; Accepted August 6, 2007. Address correspondence and reprint requests to Stephan Storch, Department of Biochemistry, Children's Hospital, University Medical Center Hamburg, D-20246 Hamburg, Germany. E-mail: storch@uke.uni-hamburg.deAbbrevations used: ACP2, human acid phosphatase 2; ACP5, human acid phosphatase 5; ACTB, human b-actin; ActB, mouse b-actin; JNCL, juvenile form of neuronal ceroid lipofuscinosis; LAMP-1, lysosomeassociated membrane protein 1; LAMP-2, lysosome-associated membrane protein 2; LAP, lysosomal acid phosphatase; M6P, mannose 6-phosphate; P week, postnatal week; RT, real-time; siRNA, small interfering RNA; TRAP, tartrate-resistant acid phosphatase.

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“…Many biochemical changes have been observed in tissues from NCL patients or affected animals; see, for example, Keller et al (1984), Wolfe et al (1987), Faisal Khan et al (1995), Katz and Siakotos (1995) and Siakotos et al (1995). However, it is not clear whether these changes represent primary cellular defects or are secondary events of the disease process.…”

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confidence: 94%

Recent advances in the molecular genetics of the neuronal ceroid lipofuscinoses

Mole

1996

J of Inher Metab Disea

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Major advances in the molecular genetic analysis of the neuronal ceroid lipofuscinoses (NCL) have recently been made: the genes for two major types have been identified and the chromosomal location for a third defined. CLN1, the gene for infantile NCL (Santavuori-Haltia disease) encodes palmitoyl protein thioesterase (PPT). Most patients (75% of disease chromosomes) have the same point mutation. In contrast, CLN3, the gene for juvenile NCL (Batten or Spielmeyer-Vogt-Sjögren disease) is not a previously known gene, nor does its product display homology to any previously described proteins. The same 1 kb genomic deletion is present in the majority of patients (81% of disease chromosomes). CLN5, the gene for Finnish variant late infantile NCL, has been mapped to 13q and should be identified in the near future. The gene for late-infantile NCL (Jansky-Bielschowsky disease) has not yet been localized to a chromosome despite intensive research. It is likely that this type of NCL is caused by mutations in more than one gene each resulting in the same phenotype.

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Abnormal acid phosphatases in neuronal ceroid‐lipofuscinoses

Cited by 8 publications

References 21 publications

Development of a simple and sensitive fluorimetric method for isolation of coumaphos-hydrolysing bacteria

Development of a simple and sensitive fluorimetric method for isolation of coumaphos-hydrolysing bacteria

Increased expression of lysosomal acid phosphatase in CLN3‐defective cells and mouse brain tissue

Recent advances in the molecular genetics of the neuronal ceroid lipofuscinoses

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