Expression of cholinesterases in human kidney and its variation in renal cell carcinoma types

Abstract

Despite the aberrant expression of cholinesterases in tumours, the question of their possible contribution to tumorigenesis remains unsolved. The identification in kidney of a cholinergic system has paved the way to functional studies, but details on renal cholinesterases are still lacking. To fill the gap and to determine whether cholinesterases are abnormally expressed in renal tumours, paired pieces of normal kidney and renal cell carcinomas (RCCs) were compared for cholinesterase activity and mRNA levels. In studies with papillary RCC (pRCC), conventional RCC, chromophobe RCC, and renal oncocytoma, acetylcholinesterase activity increased in pRCC (3.92 ± 3.01 mUAEmg )1 , P = 0.031) and conventional RCC (2.64 ± 1.49 mUAEmg , P = 0.031). Glycosylphosphatidylinositollinked acetylcholinesterase dimers and hydrophilic butyrylcholinesterase tetramers predominated in control and cancerous kidney. Acetylcholinesterase mRNAs with exons E1c and E1e, 3¢-alternative T, H and R acetylcholinesterase mRNAs and butyrylcholinesterase mRNA were identified in kidney. The levels of acetylcholinesterase and butyrylcholinesterase mRNAs were nearly 1000-fold lower in human kidney than in colon. Whereas kidney and renal tumours showed comparable levels of acetylcholinesterase mRNA, the content of butyrylcholinesterase mRNA was increased 10-fold in pRCC. The presence of acetylcholinesterase and butyrylcholinesterase mRNAs in kidney supports their synthesis in the organ itself, and the prevalence of glycosylphosphatidylinositol-anchored acetylcholinesterase explains the splicing to acetylcholinesterase-H mRNA. The consequences of butyrylcholinesterase upregulation for pRCC growth are discussed.

Acetylcholinesterase is associated with a decrease in cell proliferation of hepatocellular carcinoma cells

“…This seems to be the case for metastasized lymph node as the result of breast cancer [31], as well as for colon cancer [32], and some lung tumor types [33]. However, the relation of low AChE activity with malignancy is not so obvious reminding the enhanced AChE activity observed in some thymoma classes [34] and renal cell carcinoma types [11], which in turn highlights how complex the variation of AChE expression can be in cancerous tissues.…”

“…In addition, BuChE can also exert non-catalytic actions, as judged by the role of the BuChE-K-apolipoprotein Eε4-amyloid β-peptide complex in Alzheimer, and of BuChE itself in megakaryocytopoiesis suppression and retinal cell differentiation [11,12]. Through non-catalytic actions, AChE seems to participate directly or indirectly in motility, Fig.…”

“…Experimental evidence links these non-catalytic actions with the binding of ChEs with several protein partners. Thus, it has been reported that AChE can interact with laminins and collagen IV, amyloid β-peptide and presenilin-1, neuronal enolase, the scaffold protein RACK1 and PKC, the co-repressor CtBP, the Ran-binding protein, and a peptide fragment of AChE with nAChR [11].…”

Acetylcholinesterase overexpression mediated by oncolytic adenovirus exhibited potent anti-tumor effect

“…Besides its canonical functions, ACh can also over-activate the nicotinic acetylcholine receptor, which leads to angiogenesis, migration and proliferation of cancer cells [1, 2]. Abnormal expression of AChE protein was found in several types of cancer [3, 4]. Hepatocellular carcinoma patients with low expression of AChE exhibited poor prognosis [5].…”

Interaction of Human Brain Acetylcholinesterase with Cyclophosphamide: A Molecular Modeling and Docking Study

“…As an enzyme, the primary physiological role of AChE involves the termination of chemical transmission at cholinergic synapses and secretory organs by catalyzing the hydrolysis of the neurotransmitter acetylcholine, ACh, at a high turnover rate that approaches 2.5×10 4 molecules per second. Numerous roles have been attributed to AChE in diseases of high priority research, as in cancer [4] and Alzheimer's disease (AD) [5], to name a few. Inhibitors of AChE have been demonstrated to have efficacy (e.g., donepezil, rivastigmine and galantamine in AD; and pyridostigmine in myasthenia gravis) [6, 7] as well as toxicity (e.g., organophosphate and carbamate pesticides in health) [8], depending on their time-dependent concentration, mechanism of binding and use.…”