ABSTRACT
Maitotoxin (MTX) is the most potent marine toxin known to date. It is responsible for a particular human intoxication syndrome called ciguatera fish poisoning (CFP). Several reports indicate that MTX is an activator of non-selective cation channels (NSCC) in different cell types. The molecular identity of these channels is still an unresolved topic, and it has been proposed that the transient receptor potential (TRP) channels are involved in this effect. In Xenopus laevis oocytes, MTX at picomolar (pM) concentrations induces the activation of NSCC with functional and pharmacological properties that resemble the activity of TRP channels. The purpose of this study was to characterize the molecular identity of the TRP channel involved in the MTX response, using the small interference RNA (siRNA) approach and the two-electrode voltage-clamp technique (TEVC). The injection of a specifically designed siRNA to silence the transient receptor potential canonical type 1 (TRPC1) protein expression abolished the MTX response. MTX had no effect on oocytes, even at doses 20-fold higher compared to cells without injection. Total mRNA and protein levels of TRPC1 were notably diminished. The TRPC4 siRNA did not change the MTX effect, even though it was important to note that the protein level was reduced by the silencing of TRPC4. Our results suggest that MTX could be a selective activator of TRPC1 channels in X. laevis oocytes and a useful pharmacological tool for further studies on these TRP channels.
Subject(s)
Marine Toxins/pharmacology , Oocytes/drug effects , Oxocins/pharmacology , TRPC Cation Channels/metabolism , Xenopus , Animals , Electric Stimulation , Electrophysiology , Membrane Potentials/drug effects , Oocytes/metabolism , Patch-Clamp Techniques , TRPC Cation Channels/geneticsABSTRACT
Resumen Uno de los signos más comunes de numerosas enfermedades humanas, particularmente las infecciosas, es la fiebre caracterizada por una temperatura generalmente tomada en la piel y superior a 37° C. Históricamente, la fiebre ha sido considerada un signo de la enfermedad misma, pero estudios recientes en el campo de la Medicina Evolutiva, sugieren que la fiebre también es un mecanismo por el cual el organismo lucha contra invasores externos. Se hace una revisión de los conceptos modernos de la fiebre como base para sugerir al médico clínico, poner atención a la fiebre y no eliminarla, evitando el uso de antipiréticos sin evaluar sus posibles efectos benéficos.
Abstract One of the most common signs of numerous human diseases, especially infectious ones, is fever, characterized by a temperature generally taken on the skin and higher than 37° C. Historically, fever has been considered a sign of the disease itself. However, recent studies suggested by Evolutive Medicine view, indicate that fever is also a mechanism through which the organism fights external invaders. Here we review the modern concepts about fever as a basis to suggest clinicians to pay attention to fever, avoiding the use of antipyretics to eliminate it, without assessing its possible benefitial effects.
ABSTRACT
Resumen La Medicina Evolutiva es un enfoque al estudio de la medicina propuesto en 1994 por Randolph Nesse y George Williams, médico y biólogo evolucionista respectivamente. Aunque la evolución es una observación hecha desde hace miles de años, fue hasta que Charles Darwin describió el mecanismo que la impulsa, llamado Selección Natural y que este fue complementado con las leyes de la herencia de Gregor Mendel y los estudios que dieron origen a la genética, que su enfoque médico es aceptado. Aunque actualmente su aplicación es limitada, varias escuelas de medicina en los Estados Unidos y Europa tienen ya programas y departamentos especializados en este enfoque al estudio de la medicina. Su propósito principal es entender el origen evolutivo de las enfermedades para mejorar el cuidado y tratamiento de los pacientes. Una materia optativa sobre Medicina Evolutiva está accesible para estudiantes de la Facultad de Medicina de la UNAM.
Abstract Evolutionary medicine is an approach to the study of medicine proposed by Randolph Nesse y George Williams, physician and evolutionary biologist, respectively, in 1994. Although evolution is an observation performed since thousands of years ago, it was until Charles Darwin described the mechanism driving it, called Natural selection, which was complemented with Mendel's laws of inheritance and the studies that gave birth to genetics, that its medical approach was accepted. Although its current application is limited, several American and European medical schools have their programs and departments specialized in this approach for the study of medicine. Its main objective is to understand the evolutionary origin of diseases to improve patient's care and treatment. A free-choice subject on Evolutionary Medicine is available for the students of the Facultad de Medicina de la UNAM.
