Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Loss of lysosomal integrity is a critical event for killing tumor cells in the photodynamic therapy of cancers. To elucidate the mechanism of photodamage induced lysosomal disintegration, we investigated the role of losing lysosomal proton translocation in latency loss of photosensitized lysosomes. Isolated rat liver lysosomes were light exposed in the presence of Methylene blue. Through monitoring lysosomal delta pH with Acridine orange and measuring its membrane potential with 3,3'-dipropylthiadicarbocyanine iodide, loss of Mg-ATP dependent proton translocation and decrease in electrogenicity of the proton pump were observed after lysosomes were photosensitized. When normal lysosomes were incubated for 60 min in K+ contained medium, percentage free activity of lysosomal enzyme beta-galactosidase increased, i.e. lysosomal latency decreased. In the presence of Mg-ATP, the latency loss of incubated lysosomes reduced. Addition of n-ethylmaleimide, a potent inhibitor of lysosomal H(+)-ATPase, abolished the effect of Mg-ATP on lysosomal latency. It suggests a role of proton translocation in protecting lysosomal integrity. Under the same conditions, Methylene blue photosensitized lysosomes increasingly lost latency of beta-hexosaminidase and beta-galactosidase with light exposure, presumably due to the photodamage induced loss of proton pumping. In contrast, the photosensitization did not decrease lysosomal latency in the absence of Mg-ATP, implying that lysosomal integrity might not be impaired via other photodamage effects under the conditions of this study. These results indicate that lysosomal integrity can be photodestructed via the loss of proton translocation.
 ...
PMID:Loss of lysosomal integrity caused by the decrease of proton translocation in methylene blue-mediated photosensitization. 886 12

Methylene blue plus visible light (MB+VL) results in oxidative DNA damage, producing predominantly 7,8-dihydroxy-8-oxoguanine and other single base modifications that are repaired by base excision repair (BER). AdCA17 is non-replicating recombinant human adenovirus that infects human cells and expresses the beta-galactosidase (beta-gal) reporter gene. We have examined host cell reactivation (HCR) of beta-gal activity for (MB+VL)-treated AdCA17 in cells from patients with xeoroderma pigmentosum from complementation group C (XP-C). HCR was substantially reduced in an SV40 transformed XP-C fibroblast compared to two SV40-transformed normal cells and in three XP-C primary fibroblast strains compared to four normal strains for both untreated and UVC-treated cells. These results indicate an involvement of the XPC gene in BER of MB+VL-induced oxidative DNA damage. In addition, pre-UVC-treatment of both normal and XP-C fibroblasts resulted in enhanced HCR of the MB+VL-treated reporter gene giving evidence for a UVC-inducible and XPC-independent BER pathway in human cells.
 ...
PMID:Deficient base excision repair of oxidative DNA damage induced by methylene blue plus visible light in xeroderma pigmentosum group C fibroblasts. 1757 42

Methylene blue (MB) acts as a photosensitizer and after excitation by visible light (VL) produces reactive oxygen species that result in oxidatively damaged DNA. (MB + VL) produces predominantly 8-hydroxyguanine as well as other single base modifications in DNA that are repaired by base excision repair (BER). We have used a recombinant non-replicating human adenovirus, Ad5HCMVlacZ, which expresses the beta-galactosidase (beta-gal) reporter gene, to examine the role of the p53 tumor suppressor in constitutive and inducible BER of MB + VL-damaged DNA in human cells. Host cell reactivation (HCR) of beta-gal activity for MB + VL-treated Ad5HCMVlacZ was examined in normal human fibroblasts and several transformed and tumor cell lines with compromised p53 function using both non-treated cells and cells pretreated with ultraviolet light of 200-280 nm wavelength (UVC). Constitutive HCR of the MB + VL-treated reporter gene in untreated cells did not correlate with wild-type p53 expression levels, suggesting that factors other than p53 expression levels can influence constitutive BER of the reporter gene. UVC pre-treatment of the normal fibroblast strains resulted in an enhanced HCR of the MB + VL-treated reporter gene and a concomitant increase in the expression of p53, suggesting that p53 may be involved in UV-inducible BER in normal human fibroblasts. In contrast, p53 expression did not correlate with HCR values for the p53-compromised cells in UVC-pre-treated cells. In particular, the SKOV-3, LFS 087 and NF-E6 cells showed no up-regulation of p53 expression following UVC, and yet these cells showed significant enhancement of HCR following UVC pre-treatment. These results indicate that BER of MB + VL-damaged DNA is inducible in human cells by pre-UVC treatment and that the enhancement in BER may result from both p53-dependent and p53-independent mechanisms.
 ...
PMID:UV-inducible base excision repair of oxidative damaged DNA in human cells. 1883 99