The identification of novel anti-apoptotic sequences has lead to new insights into the mechanisms involved in regulating different forms of programmed cell death. For example, the anti-apoptotic function of free radical scavenging proteins supports the pro-apoptotic function of Reactive Oxygen Species (ROS). Using yeast as a model of eukaryotic mitochondrial apoptosis, we show that a cDNA corresponding to the mitochondrial variant of the human DUT gene (DUT-M) encoding the deoxyuridine triphosphatase (dUTPase) enzyme can prevent apoptosis in yeast in response to internal (Bax expression) and to exogenous (H(2)O(2) and cadmium) stresses. Of interest, cell death was not prevented under culture conditions modeling chronological aging, suggesting that DUT-M only protects dividing cells. The anti-apoptotic function of DUT-M was confirmed by demonstrating that an increase in dUTPase protein levels is sufficient to confer increased resistance to H(2)O(2) in cultured C2C12 mouse skeletal myoblasts. Given that the function of dUTPase is to decrease the levels of dUTP, our results strongly support an emerging role for dUTP as a pro-apoptotic second messenger in the same vein as ROS and ceramide.

The ergogenic effects of caffeine ingestion (240–840 mg) on exercise performance is well established, albeit in some cases with negative side effects. However, recent evidence shows that much smaller doses can have beneficial effect on endurance performance as well as on mental function. Less is known about the possible synergistic effects of low dose of caffeine (CAF) and carbohydrate (CHO) feedings, especially as related to team sports performance. PURPOSE: To determine the effects of low dose (100 mg) CAF ingestion along with typically recommended CHO on physical and mental function during intermittent high intensity exercise that mimics the demands of competitive team sports. METHODS: Physically active male (N=6) and female (N=4) low to moderate caffeine users participated in this study. Experimental trials consisted of four ∼22-minute quarters (QTR) of shuttle running. Physical and mental function tests were administered throughout the experimental trial including (20-m sprint, vertical jump, gross motor skill test, force sensation, rating of perceived exertion, profile of mood states and psychomotor vigilance test).On four separate occasions, subjects received 20-oz of flavored water placebo (PLA), CHO, PLA+CAF and CHO+CAF prior to exercise. During exercise, subjects ingest PLA, CHO, PLA and CHO respectively (3.5 ml·kg-1). RESULTS: No difference was found in 20-m sprint time, vertical jump and gross motor skills performance between any treatments. However, both caffeine treatments (PLA+CAF and CHO+CAF) significantly improved psychomotor vigilance and reduced force sensation at HALFTIME (p<0.05). CHO+CAF also improved self-reported perception of fatigue, vigor and overall mood compared to PLA+CAF (p<0.05). Systolic blood pressure was increased with CHO+CAF compare to other three treatments. However, no difference was found in heart rate, core body temperature, plasma volume change, or hydration status between any treatments. CONCLUSION: The data suggest that ingestion of a low dose of caffeine prior to exercise did not add to the expected benefits of CHO feedings alone on physical tasks. However, all of the mental function tasks were significantly enhanced with the combination of CHO plus CAF, with little or no adverse side effects. Funded by Gatorade Sports Science Institute.