ABSTRACT
BACKGROUND: In normal prostate epithelial cells low m-aconitase activity decreases citrate oxidation leading to citrate accumulation. In prostate cancer cells m-aconitase activity is increased and citrate content is lower. The effect of inhibition of m-aconitase on ATP production by prostate cancer cells (PC3) is not known nor is the contribution of glycolysis versus respiration. METHODS: ATP content of PC3 cells as affected by inhibition of m-aconitase (fluoroacetate (FA), zinc), inhibition of glycolysis (2DxG), or respiration (DNP, oligomycin) was determined. The ability to maintain ATP using glucose or glutamine as sole substrate was also determined. Intermediates including ATP, lactate, glucose, and glutamine were assayed in neutralized perchloric acid (PCA) cell extracts, virgin, and conditioned medium by enzymatic fluorometry. RESULTS: Data show that inhibition of m-aconitase, glycolysis, or respiration alone did not decrease ATP content. Inhibition of both glycolysis and respiration were required to decrease ATP content. PC3 cells were able to produce ATP with either glucose or glutamine as sole substrate. Though FA clearly inhibited m-aconitase there was no evidence that zinc had a similar effect. CONCLUSION: PC3 cells can support ATP production when m-aconitase is inhibited by using glycolysis or oxidation of substrate (e.g., glutamine) entering the TCA cycle distal to citrate.
Subject(s)
Adenosine Triphosphate/analysis , Antimetabolites/pharmacology , Citric Acid/analysis , Prostatic Neoplasms/chemistry , Aconitate Hydratase/antagonists & inhibitors , Cell Line, Tumor , Deoxyglucose/pharmacology , Dinitrophenols/pharmacology , Enzyme Inhibitors/pharmacology , Fluoroacetates/pharmacology , Glycolysis/drug effects , Humans , Male , Oligomycins/pharmacology , Oxygen Consumption/drug effects , Zinc/pharmacologySubject(s)
Clavicle , Skin Transplantation/methods , Carcinoma, Basal Cell/surgery , Cicatrix/prevention & control , Dermatologic Surgical Procedures , Elasticity , Humans , Mohs Surgery/rehabilitation , Skin Neoplasms/surgery , Skin Physiological Phenomena , Skin Transplantation/pathology , Suture Techniques/instrumentationSubject(s)
Tattooing/trends , Adult , Age Factors , Costs and Cost Analysis , Data Interpretation, Statistical , Humans , Tattooing/economicsABSTRACT
We report a 16-year-old Hispanic girl with gastrointestinal complaints and an unusual cutaneous eruption consisting of vesiculopustules and blanching erythematous plaques with peripheral scale. Diagnostic workup showed collections of neutrophils in the upper epidermis and subcorneal layer on the skin biopsy specimen, and deep ulcerations, crypt abscesses, and granulomas on endoscopy, diagnostic of Crohn disease. The skin findings are consistent with a vesiculopustular eruption without vasculitis, previously only reported in association with ulcerative colitis. This case broadens the spectrum of neutrophil-based cutaneous disorders associated with inflammatory bowel disease. Clinicians should be aware of the usual cutaneous manifestations of inflammatory bowel disease and consider the diagnosis of Crohn disease in the context of vesiculopustular dermatitis and abdominal symptomatology.
