Cell Biology Symposium
By: Nicole Tillquist
Dr. Danica Chen kicked off the Cell Biology Symposium with the presentation of Mitochondrial Metabolic Checkpoint, Stem Cell Aging, and Rejuvenation by introducing the topic of age. Dr. Chen’s lab is primarily interested in understanding how we age, and more specifically if the cause of aging reversible. Intrigued by a study that focused on hematopoietic stem cells, Dr. Chen’s research focuses on using methods of biochemistry to map metabolic pathways to help understanding and function of aging. Dr. Chen’s research specifically looked at uncovering a better interpretation of mitochondrial unfolded protein response, which is facilitated by the interaction of SIRT7 and NRF1. Inactivation of SIRT7 caused an increase in mitochondrial protein folding stress and the regenerative capacity of hematopoietic stem cells was compromised. Chen mentioned a good rule of thumb when working with mice models; “try aging the mouse if you aren’t getting the phenotype you’re looking for”. SIRT7 expression is reduced in aged hematopoietic stem cells, and SIRT7 up-regulation improved the regenerative capacity. These findings define the deregulation of a mitochondrial unfolded protein response -mediated metabolic checkpoint as a reversible contributing factor for hematopoietic stem cells aging. Other data supports the idea that this regulatory mechanism can be applied across other tissues.
Dr. Fernando J. Pena continued the discussion of oxidative stress but introduced us to the impact it can have on spermatozoa in the world of equine. Dr. Pena’s presentation on Redox Regulation of Stallion Spermatozoa: impact on reproductive technologies began with the osmotic effects that cryopreservation has on spermatozoa. There is an increase in extracellular osmolarity during freezing and a decrease during thawing. It is during the thawing process that acute necrosis can occur resulting in decreased fertility. Redox signaling is an important mechanism that spermatozoa use to respond to different environments. Reactions of oxygen and reduction play major roles in many aspects of spermatozoa. These reactions impact not only the lipid of the membranes and DNA but also the proteins which can have regulatory functions in the sperm. Roughly 90% of reactive oxygen species (ROS) are produced in the mitochondria, and before now it wasn’t a standard to look at the mitochondria in equine. However, recent research indicates that sperm mitochondria are vital structures in sperm function and are compromised during cryopreservation. Dr. Pena explained that the addition of antioxidants was successful in some species to control for ROS but was not successful in equine. Dr. Pena then described his research which focused on improving the quality of the mitochondria of the surviving spermatozoa post-thawing and discussed the future research involving proteomics.
Dr. Marie-France Palin gave her presentation on Carnosine prevents oxidative damage in myoblast cells derived from porcine skeletal muscle. This presentation tied in well with the theme of oxidative stress while giving us a new species to relate the information to. Dr. Palin started with describing the importance of carnosine, which was the first bioactive peptide identified. Dr. Palin went through the different properties of carnosine, specifically that it is higher in glycolytic or “white” muscles. This fact is important when discussing research involving porcine because pigs have a large proportion of white muscles. Carnosine is not found in plants and in most countries, pigs are fed a vegetarian diet, so pigs do not get carnosine in their diet. A Previous study reported changes in meat quality through supplementation in pigs but failed to report their initial muscle concentrations so a direct link between carnosine supplementation and meat quality could not be made. Dr. Palin’s research fills in that missing link and looked at muscle carnosine in different pig breeds and studied the effect of different muscle carnosine content on meat quality. Results showed a difference in carnosine concentration between breed. Duroc showed the highest concentration. Pigs came from 16 different farms, all had the same diet and management so only variable factor was their genetic background. Meat color, water holding capacity, pH, shear force (tenderness measure), and glycolytic potential were used to determine meat quality. With a higher concentration of carnosine in muscle, meat quality was improved. Dr. Palin then went on to describe the second study that used a cell culture model to explore the effect of oxidative stress and how varying doses of carnosine can increase viability and proliferation in myoblast cells.
To wrap the symposium, Dr. Josh Selsby discussed heat stress in skeletal muscle and the radical changes that are induced. Dr. Selsby discussed how heat stress has a direct impact on meat production and meat quality. Dr. Selsby also linked these impacts to human and animal health and the threat to food security. One interesting statement made is that currently cooling is one of the only treatments used for heat stress and the question to keep in mind with cooling is does it offset the damage? The question of how heat affects mitochondria were also brought up, with the explanation being an increase in electron leakage, oxidative stress, and free radicals. Dr. Selsby presented extensive research showing a definite increase in oxidative stress at a time of 2 hours of heat stress, and interestingly a decline at 4 hours through 6 hours landing in the thermoneutral zone. Dr. Selsby stated that if heat stress is constant, then there must be a pathway that is responding to the heat stress by removing damaged mitochondria or damaged parts of mitochondria via autophagy/mitophagy. Dr. Selsby concludes that maintaining a functional mitochondrial pool is essential to mitigate heat stress-mediated dysfunction.