Cover Letter N°2

Dr. Frank W. Booth
Editor-in-Chief, JBC
Department of Medical Pharmacology and Physiology
University of Missouri, Columbia


Dear Dr. Booth:

We are submitting our work titled “Extracelullar ATP, ADP or adenosine stimulation induces gene expression in rat skeletal myotubes” to the Journal of Biological Chemistry (JBC). The article is authored by Rodrigo Fernández, Sonia Buvinic and Enrique Jaimovich, all members of the Muscle Cellular Physiology Laboratory from the University of Chile. The study shows that P2Y1 and adenosine receptors activation leads to gene-expression in skeletal myotubes, suggesting their participation in the slow calcium signaling pathway.
Our laboratory has dedicated to identify completely one of the signaling pathways activated during muscle contraction, named slow calcium signaling pathway. Recently, we showed that contracting skeletal myotubes release ATP, and that it leads to gene-expression. However, the receptors involved were unknown. This study was designed to identify what extracellular receptors are activated by ATP. We found that P2Y1 and adenosine receptors activation induced a gene-expression pattern similar to what we had previously shown in response to contraction. These results increase our knowledge about the slow calcium signaling pathway. In the future, we will be able to identify the contraction characteristics that an exercise needs to fulfill to activate this pathway. Then it will be possible to prescribe that exercise to people who specifically need the proteins expressed through the pathway to improve their health. Also, it will be possible to develop drugs that specifically activate the pathway to increase the protein synthesis in those people who cannot exercise.
The article has not been submitted for publication elsewhere, and there are not conflicts of interests.

Sincerely
Rodrigo Fernández

Corresponding author:
Rodrigo Fernández
E-mail: rfernandez@uchile.cl

Cover Letter N°1

Dear Dr. Booth

We are submitting our work titled “Extracellular ATP, ADP or adenosine stimulation induces gene expression in skeletal miotubes” to the Journal of Biological Chemistry. The work’s authors are Lic. Rodrigo Fernández, PhD Sonia Buvinic and PhD Enrique Jaimovich, all members of the Muscle Cellular Physiology Laboratory from the University of Chile. Our research was designated to increase our understanding of the slow calcium signaling pathway in muscle cells, through the identification of some extracellular receptors involved on it, which activation leads to gene expression.
We showed that specific activation of P2Y1 and adenosine receptors can resemble some of the genetic expression induced by contraction of muscle cells, probably activating the slow calcium signaling pathway. It is so important because if we unravel the complete pathway, then we will be able to found the better exercise protocol that leads to its activation and the gene expression derived of it, so we can prescribe this exercise to the people who precisely need to express that proteins. On the other hand, there will be the possibility to design pharmaceutical agents that can activate the pathway for those people who can not exercise.
The article has not been submitted for publication elsewhere, and there are not conflict of interests.

Sincerely

Lic. Rodrigo Fernández
MSc student at the University of Chile
For contact write to rodrigo@med.uchile.cl

Education system’s aim, is it unfocused?

It is surprising when one listen the talk and think how right it is in some aspects. Maybe the situation described there had happened to us, and we finally have decided to follow the way that the education system has prepared to us. I do not think it is the wrong way to do things, actually, this system has brought the scientific knowledge to a higher level that let us, for example, to have a better quality and longer life. However, I agree that we need to incorporate other types of capacities into our lives; music, art, and others, would help us to be more integral persons. But I think scientific development also needs to have a high level of creativity. Much of the greatest discoveries are due to brilliant ideas, and I think creativity is the basis for them. Creativity is everywhere, in music, art and also in science, and we have to use it the best as we can to build a better world for everyone.

Extracellular ATP, ADP or adenosine stimulation induces gene expression in skeletal miotubes

Skeletal muscle activation induces a slow calcium signal which is associated with gene expression. It has been shown that the release of ATP from muscle cells participates in the signal transduction pathway that induces this response. However, the specific receptors involved are still unknown. The aim of this study was to gain a first insight into the receptors involved in this gene expression signaling pathway. Rat skeletal miotubes were incubated with specific receptors agonists (ATP, ADP, UTP, UDP and adenosine) at different concentrations. Thereafter, interleukin-6 (IL-6) and c-fos mRNAs were analyzed with the RT-PCR method to determine the gene expression response to different extracellular receptors activation. High ATP (all P2Y and P2X purinergic receptors subtypes) concentrations induced increases in the gene expression of both IL-6 and c-fos, while high ADP (P2Y1 receptor) concentrations only induced increases in IL-6 mRNA. Neither UTP (receptors P2Y2 and P2Y4) nor UDP (receptor P2Y6) induced gene expression. Stimulation with adenosine (specific adenosine receptors) instead, showed a time and concentration dependent gene expression response, increasing mRNA for both IL-6 and c-fos but under different conditions. Thus, the results show that P2Y1 and adenosine receptors activation leads to gene expression, suggesting the participation of these receptors in the slow calcium signaling pathway.

Key words: slow calcium signal, nucleotide receptors, interleukin-6, c-fos

Extracellular ATP, ADP or adenosine stimulation induces gene expression in skeletal miotubes

Skeletal muscle activation induces a slow calcium signal which is associated with gene expression. It has been shown that the release of ATP from cells participates in the signal transduction pathway that induces this response, but the specific receptors involved are unknown. The aim of this study was to gain a first insight into the receptors involved in this gene expression signaling pathway. Rat skeletal miotubes were incubated with specific receptors agonists (ATP, ADP, UTP, UDP and adenosine) at different concentrations. Thereafter, interleukin-6 (IL-6) and c-fos mRNAs were analyzed with the RT-PCR method to determine the gene expression response to different extracellular receptors activation. High ATP (all P2Y and P2X purinergic receptors subtypes) concentrations induced increases in the gene expression of both IL-6 and c-fos, while high ADP (P2Y1 receptor) concentrations only induced increases in IL-6 mRNA. Neither UTP (receptors P2Y2 and P2Y4) nor UDP (receptor P2Y6) induced gene expression. Stimulation with adenosine (specific adenosine receptors) instead, showed a time and concentration dependent gene expression response, increasing mRNA for both IL-6 and c-fos but under different conditions. Thus, the results show that P2Y1 and adenosine receptors activation leads to gene expression, suggesting their participation in the slow calcium signaling pathway.

Key words: slow calcium signal, nucleotide receptors, interleukin-6, c-fos

Extracellular ATP, ADP or adenosine stimulation induces gene expression in skeletal miotubes

Skeletal muscle activation induces a slow calcium signal which is associated with gene expression. It has been shown that the release of ATP from cells participates in the signal transduction pathway that induces this response, but the specific receptors involved are unknown. The aim of this study was to gain a first insight into the receptors involved in this gene expression signaling pathway. Rat skeletal miotubes were incubated with specific receptors agonists (ATP, ADP, UTP, UDP and adenosine) at different concentrations. Thereafter, interleukin-6 (IL-6) and c-fos mRNAs were analyzed through the RT-PCR method, to determine the gene expression response to different extracellular receptors activation. High ATP (activates all purinergic receptors) concentrations induced increases in the gene expression of both IL-6 and c-fos, while high ADP (P2Y1 receptor) concentrations only induced increases in IL-6 mRNA. Neither UTP (receptors P2Y2 and P2Y4) nor UDP (receptor P2Y6) induced gene expression. Stimulation with adenosine (specific adenosine receptors) instead, showed a time and concentration dependent gene expression response, increasing mRNA for both IL-6 and c-fos but under different conditions. Thus, the results show that P2Y1 and adenosine receptors activation leads to gene expression, suggesting their participation in the slow calcium signaling pathway.

Key words: slow calcium signal, nucleotide receptors, interleukin-6, c-fos

Extracellular ATP, ADP and adenosine stimulation induces gene expression in skeletal miotubes

Skeletal muscle activation induces a slow calcium transient which is associated with gene expression. There has been shown that the release of ATP from cells participates in the signal transduction pathway that induces this response, but the specific receptors involved are unknown. The aim of this study was to gain a first insight into the receptors involved in this gene expression signaling pathway. Rat skeletal miotubes were incubated with specific receptors agonists (ATP, ADP, UTP, UDP and adenosine) at different concentrations. Thereafter, interleukin-6 (IL-6) and c-fos mRNAs were analyzed through the RT-PCR method, to determine the gene expression response to different extracellular receptors activation. High ATP (activates all purinergic receptors) concentrations induced increases in the gene expression of both IL-6 and c-fos, while high ADP (P2Y1 receptor) concentrations only induced increases in IL-6 mRNA. Neither UTP (receptors P2Y2 and P2Y4) nor UDP (receptor P2Y6) induced gene expression. Stimulation with adenosine (specific adenosine receptors) instead, showed a time and concentration gene expression response, increasing mRNA for both IL-6 and c-fos but under different conditions. Thus, the results show that P2Y1 and adenosine receptors activation leads to gene expression, suggesting their participation in the slow calcium signaling pathway.

Key words: slow calcium signal, nucleotide receptors, interleukin-6, c-fos