The ability to sense temperature changes is crucial for mammalian survival.Mammalian thermal sensing is primarily carried out by thermosensitive transient receptor potential channels(Thermo-TRPs).Some mammals hibernat...The ability to sense temperature changes is crucial for mammalian survival.Mammalian thermal sensing is primarily carried out by thermosensitive transient receptor potential channels(Thermo-TRPs).Some mammals hibernate to survive cold winter conditions,during which time their body temperature fluctuates dramatically.However,the underlying mechanisms by which these mammals regulate thermal responses remain unclear.Using quantitative real-time polymerase chain reaction(qRT-PCR)and the Western blotting,we found that Myotis ricketti bats had high levels of heat-activated TRPs(e.g.,TRPV1 and TRPV4)during torpor in winter and cold-activated TRPs(e.g.,TRPM8 and TRPC5)during active states in summer.We also found that laboratory mice had high mRNA levels of cold-activated TRPs(e.g.,Trpm8 and Trpc5)under relatively hot conditions(i.e.,40°C).These data suggest that small mammals up-regulate the expression of cold-activated TRPs even under warm or hot conditions.Binding site analysis showed that some homeobox(HOX)transcription factors(TFs)regulate the expression of hot-and cold-activated TRP genes and that some TFs of the Pit-Oct-Unc(POU)family regulate warm-sensitive and cold-activated TRP genes.The dual-luciferase reporter assay results demonstrated that TFs HOXA9,POU3F1,and POU5F1 regulate TRPC5 expression,suggesting that Thermo-TRP genes are regulated by multiple TFs of the HOX and POU families at different levels.This study provides insights into the adaptive mechanisms underlying thermal sensing used by bats to survive hibernation.展开更多
文摘肝脏是哺乳动物基础代谢产热的关键器官。温敏瞬时受体电位通道蛋白(Thermosensitive transient receptor potential channels,Thermo-TRPs)参与了调控肝细胞的生理功能。为了解Thermo-TRPs是否参与肝脏的代谢产热,以成年布氏田鼠(Lasiopodomys brandtii)为研究对象,测定了不同驯化温度下6种Thermo-TRPs在肝脏中的表达,分析其与肝脏产热相关蛋白和信号通路蛋白的关系。结果显示:(1)与高温组相比,低温增加了肝脏解偶联蛋白1(uncoupling protein 1,UCP1)的表达;而与常温组相比,低温降低了肝脏解偶联蛋白3(uncoupling protein 3,UCP3)的表达;(2)6种Thermo-TRPs均在肝脏中表达,与高温组相比,低温显著降低了TRP vanilloid 4(TRPV4)的表达,同时显著增加了腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)的表达;(3)低温显著增加了布氏田鼠血清三碘甲状腺原氨酸(T_(3))水平,提高了T_(3)/T_(4)比值;T_(3)/T_(4)比值与肝脏UCP1和AMPK呈显著正相关,肝脏中UCP1与TRPM2和AMPK呈显著正相关。这些结果表明,肝脏TRPV4和AMPK可能参与了低温环境中代谢产热等生理功能的调节过程。
基金supported by the National Natural Science Foundation of China(31100273 to Y.H.P.and 91731304 to H.P.L.)。
文摘The ability to sense temperature changes is crucial for mammalian survival.Mammalian thermal sensing is primarily carried out by thermosensitive transient receptor potential channels(Thermo-TRPs).Some mammals hibernate to survive cold winter conditions,during which time their body temperature fluctuates dramatically.However,the underlying mechanisms by which these mammals regulate thermal responses remain unclear.Using quantitative real-time polymerase chain reaction(qRT-PCR)and the Western blotting,we found that Myotis ricketti bats had high levels of heat-activated TRPs(e.g.,TRPV1 and TRPV4)during torpor in winter and cold-activated TRPs(e.g.,TRPM8 and TRPC5)during active states in summer.We also found that laboratory mice had high mRNA levels of cold-activated TRPs(e.g.,Trpm8 and Trpc5)under relatively hot conditions(i.e.,40°C).These data suggest that small mammals up-regulate the expression of cold-activated TRPs even under warm or hot conditions.Binding site analysis showed that some homeobox(HOX)transcription factors(TFs)regulate the expression of hot-and cold-activated TRP genes and that some TFs of the Pit-Oct-Unc(POU)family regulate warm-sensitive and cold-activated TRP genes.The dual-luciferase reporter assay results demonstrated that TFs HOXA9,POU3F1,and POU5F1 regulate TRPC5 expression,suggesting that Thermo-TRP genes are regulated by multiple TFs of the HOX and POU families at different levels.This study provides insights into the adaptive mechanisms underlying thermal sensing used by bats to survive hibernation.
