1. Acute Exercise Regulates hTERT Gene Expression and Alternative Splicing in the hTERT-BAC Transgenic Mouse Model
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Slusher, Aaron L., Kim, Jeongjin JJ, Ribick, Mark, and Ludlow, Andrew T.
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Alternative Splicing ,Mice ,Physical Conditioning, Animal ,Animals ,Gene Expression ,Humans ,Mice, Transgenic ,Physical Therapy, Sports Therapy and Rehabilitation ,Orthopedics and Sports Medicine ,Telomerase ,Article - Abstract
INTRODUCTION: Aerobic exercise maintains telomere length through increased human telomerase reverse transcriptase (hTERT) expression and telomerase enzyme activity. The impact of acute exercise on hTERT alternative splicing (AS) is unknown. PURPOSE: This study aimed to examine hTERT AS in response to acute treadmill running. METHODS: A bacterial artificial chromosome mouse model containing the 54 kilobase hTERT gene locus inserted into its genome (hTERT-BAC) was utilized. The gastrocnemius, left ventricle, and brain were excised prior to (Pre), upon cessation (Post), and during recovery (1, 24, 48, and 72H; n = 5/time point) from treadmill running (30 min. at 60% max. speed). Full length (FL) hTERT and the “minus beta” (−β) AS variant (skips exons 7 and 8 and does not code for active telomerase) were measured by gel based and droplet digital RT-PCR methods. SF3B4 and SRSF2 protein expression were measured by western blotting. RESULTS: Compared to Pre, FL hTERT increased at Post before decreasing during recovery in the gastrocnemius (48 and 72H; p ≤ 0.001) and left ventricle (24 h; p = 0.004). The percentage of FL hTERT in the gastrocnemius also increased during recovery (1 and 72H; p ≤ 0.017), whereas a decrease was observed in the left ventricle (1, 24, and 48 h; p ≤ 0.041). hTERT decreased in the brain (48 h), whereas FL hTERT percentage remained unaltered. SF3B4 protein expression decreased throughout recovery in the gastrocnemius and tended to be associated with FL hTERT (r = −0.348, p = 0.075) and −β in opposite directions (r = 0.345, p = 0.067). CONCLUSIONS: Endurance exercise increased hTERT gene expression and altered FL hTERT splicing contractile tissues and may maintain telomere length necessary to improve the function and health of the organism.
- Published
- 2022
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