Acute Exercise Regulates hTERT Gene Expression and Alternative Splicing in the hTERT-BAC Transgenic Mouse Model.
Acute Exercise Regulates hTERT Gene Expression and Alternative Splicing in the hTERT-BAC Transgenic Mouse Model.
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DOI：
10.1249/mss.0000000000002868
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发表时间：
2022-06-01
影响因子：
4.1
通讯作者：
Ludlow, Andrew T.
中科院分区：
文献类型：
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作者：
Slusher, Aaron L.;Kim, Jeongjin J. J.;Ribick, Mark;Ludlow, Andrew T.
有氧运动通过增加人类端粒酶逆转录酶(HTERT)的表达和端粒酶活性来维持端粒长度。急性运动对hTERT选择性剪接(AS)的影响尚不清楚。本研究旨在检测hTERT AS对急性跑台运动的反应。利用含有54kb hTERT基因插入基因组的细菌人工染色体小鼠模型(hTERT-BAC)。分别于运动前(Pre)、停止运动后(Post)和恢复期间(1、24、48、72h；n=5/时间点)分别切取腓肠肌、左心室和脑组织。最高为60%。速度)。用凝胶和液滴数字RT-PCR法检测全长(FL)端粒酶逆转录酶(HTERT)和作为变异体的“负β”(−β)(跳过外显子7和8，不编码活性端粒酶)。免疫印迹法检测SF3B4和SRSF2蛋白表达。与治疗前相比，腓肠肌(48小时和72小时；p≤0.001)和左心室(24小时；p=0.004)的FL-hTERT在恢复期先升高后下降。在恢复期，腓肠肌FL端粒酶逆转录酶的百分比也增加(1和72h；p≤0.017)，而左心室则减少(1、24和48h；p≤0.041)。脑内hTERT减少(48h)，而FL hTERT百分比无变化。SF3B4蛋白在腓肠肌的表达在整个恢复期呈下降趋势，与FL、hTERT呈正相关(r=−0.348，p=0.075)，与−β呈反向相关(r=0.345，p=0.067)。耐力运动增加hTERT基因表达，改变FL hTERT拼接收缩组织，并可能维持改善机体功能和健康所必需的端粒长度。
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. This study aimed to examine hTERT AS in response to acute treadmill running. 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. 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). 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.