The SLC45A2 gene encodes a Membrane-Associated Transporter Protein (MATP). Mutations of this gene cause oculocutaneous albinism type 4 (OCA4). However, the molecular mechanism of its action in melanogenesis has not been elucidated. Here, we discuss the role of MATP in melanin production. The SLC45A2 gene is highly enriched in human melanocytes and melanoma cell lines, and its protein, MATP, is located in melanosomes. The knockdown of MATP using siRNAs reduced melanin content and tyrosinase activity without any morphological change in melanosomes or the expression of melanogenesis-related proteins. Interestingly, the knockdown of MATP significantly lowered the melanosomal pH, as verified through DAMP analysis, suggesting that MATP regulates melanosomal pH and therefore affects tyrosinase activity. Finally, we found that the reduction of tyrosinase activity associated with the knockdown of MATP was readily recovered by copper treatment in the in vitro L-DOPA oxidase activity assay of tyrosinase. Considering that copper is an important element for tyrosinase activity and that its binding to tyrosinase depends on melanosomal pH, MATP may play an important role in regulating tyrosinase activity via controlling melanosomal pH.
In order to study the clinicopathologic characteristics of the clear cell variant of hepatocellular carcinoma (HCC), 215 consecutive cases measuring less than 5 cm in diameter were reviewed. The cases were divided into clear cell HCC (20 cases); focal clear cell HCC (77 cases); and non-clear cell HCC (118 cases). Clinical and pathological findings were compared among these groups. Clear cell HCC was moderately differentiated in 80% of cases and the incidence was not related to tumor size. The male to female ratio was 2.3:1, lower than the 6.9:1 of non-clear cell HCC. The association rate with liver cirrhosis was 90%, higher than the 59.3% of non-clear cell HCC. Three- and five-year survival rates, and no recurrence time were 54.5%, 33.3%, and 564 days, respectively, lower than the findings of 74.3%, 46.1%, and 770 days for non-clear cell HCC. But there is no significant difference in prognosis between both groups. Ultrastructurally, clear cells showed abundant glycogen storage and a variable degree of fat vacuoles, with a marked reduction of the number and size of organelles in the 8 cases examined. Non-clear cells of focal clear cell and non-clear cell HCC showed a moderate degree of glycogen storage in 85.7% and 28.6% of the seven cases examined from each group, with significant difference. It was concluded that clear cell HCC occurs mostly in the moderately differentiated form and is characterized by high female prevalence, high rate of association with liver cirrhosis, and has no significant difference in prognosis compared with non-clear cell HCC.
The prevalence (90%) of the BRAF (V600E) mutation in this study is the highest ever reported, confirming the key role of this mutation in PTC tumorigenesis. The BRAF (V600E) mutation was associated with aggressive clinical behaviors including extrathyroid invasion, lymph nodal metastasis and tumor multifocality. The PNA clamp real-time PCR method for the BRAF (V600E) mutation detection is sensitive and is applicable in a clinical setting.
Chronic redox imbalance in erythrocytes of individuals with sickle cell disease (SCD) contributes to oxidative stress and likely underlies common etiologies of hemolysis. We measured the amounts of six antioxidant enzymes-SOD1, catalase, glutathione peroxidase 1 (GPx1), as well as peroxiredoxins (Prxs) I, II, and VI-in red blood cells (RBCs) of SCD patients and control subjects. The amounts of SOD1 and Prx VI were reduced by about 17% and 20%, respectively, in SCD RBCs compared with control cells. The amounts of Prx II and GPx1 did not differ between SCD and normal RBCs. However, about 18% of Prx II was inactivated in SCD RBCs as a result of oxidation to sulfinic Prx II, whereas inactive Prx II was virtually undetectable in control cells. Furthermore, GPx1 activity was reduced by about 33% in SCD RBCs, and the loss of activity was correlated with hemolysis in SCD patients. RBCs from SCD patients taking hydroxyurea demonstrated 90% higher GPx1 activity than did those from untreated SCD patients, with no differences seen for the other catalytic antioxidants. Hydroxyurea induced GPx1 expression in multiple cultured cell lines in a manner dependent on both p53 and NO-cGMP signaling pathways. GPx1 expression represents a previously unrecognized potential benefit of hydroxyurea treatment in SCD patients. Antioxid. Redox Signal. 13, 1-11.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.