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Sphingomyelin synthase 1 (SMS1) and SMS2 are two isoforms of SMS, the last enzyme for sphingomyelin (SM) biosynthesis. To evaluate the role of SMS in vivo in terms of plasma lipoprotein metabolism, we generated recombinant adenovirus vectors containing human SMS1 cDNA (AdV-SMS1), SMS2 cDNA (AdV-SMS2), or the reporter LacZ cDNA (AdV-LacZ) as a control. On day 7 after intravenous infusion of 2 × 1011 particles of both AdV-SMS1 and AdV-SMS2 into mice, liver SMS1 and SMS2 mRNA levels as well as SMS activity were significantly increased (2.5-, 2.7-, 2.1-, and 2.3-fold, respectively; P < 0.001). Lipoprotein analysis indicated that AdV-SMS1 and AdV-SMS2 treatment caused no changes of total SM and cholesterol levels but significantly decreased HDL-SM and HDL-cholesterol (42% and 38%, and 27% and 25%, respectively; P < 0.05). It also significantly increased non-HDL-SM and non-HDL-cholesterol levels (50% and 35%, and 64% and 61%, respectively; P < 0.05) compared with AdV-LacZ controls. SDS-PAGE showed a significant increase in apolipoprotein B (apoB; P < 0.01) but no changes in we that both and significantly after treatment with a To the of we liver B levels that AdV-SMS1 and AdV-SMS2 liver and levels in no in increase of plasma for but for in both AdV-SMS1 and AdV-SMS2 compared with controls. SMS1 and SMS2 increased lipoprotein the increased plasma SM levels in of and in human with Sphingomyelin synthase 1 (SMS1) and SMS2 are two isoforms of SMS, the last enzyme for sphingomyelin (SM) biosynthesis. To evaluate the role of SMS in vivo in terms of plasma lipoprotein metabolism, we generated recombinant adenovirus vectors containing human SMS1 cDNA (AdV-SMS1), SMS2 cDNA (AdV-SMS2), or the reporter LacZ cDNA (AdV-LacZ) as a control. On day 7 after intravenous infusion of 2 × 1011 particles of both AdV-SMS1 and AdV-SMS2 into mice, liver SMS1 and SMS2 mRNA levels as well as SMS activity were significantly increased (2.5-, 2.7-, 2.1-, and 2.3-fold, respectively; P < 0.001). Lipoprotein analysis indicated that AdV-SMS1 and AdV-SMS2 treatment caused no changes of total SM and cholesterol levels but significantly decreased HDL-SM and HDL-cholesterol (42% and 38%, and 27% and 25%, respectively; P < 0.05). It also significantly increased non-HDL-SM and non-HDL-cholesterol levels (50% and 35%, and 64% and 61%, respectively; P < 0.05) compared with AdV-LacZ controls. SDS-PAGE showed a significant increase in apolipoprotein B (apoB; P < 0.01) but no changes in we that both and significantly after treatment with a To the of we liver B levels that AdV-SMS1 and AdV-SMS2 liver and levels in no in increase of plasma for but for in both AdV-SMS1 and AdV-SMS2 compared with controls. SMS1 and SMS2 increased lipoprotein the increased plasma SM levels in of and in human with Sphingomyelin (SM) of the in the of and of of human It for that plasma SM for sphingomyelin as a for and that in both in and in and in human in the of the in human in SM plasma containing human and of the in human SM levels in apolipoprotein are in sphingomyelin of plasma in apolipoprotein and and with and the increased in and the apolipoprotein SM levels are increased in in and and and and for the that SM decreased SM in the plasma and significantly decreased of of plasma and in of sphingomyelin in apolipoprotein that plasma SM a role in the of the of in with and cholesterol in the in in SM a of as for the of and for in of the into of the plasma of changes of SM lipoprotein metabolism, lipoprotein levels in the Sphingomyelin synthase the last enzyme in the SM that the the of SM and of the and of sphingomyelin the the that SM that SM synthase in the Sphingomyelin in liver the and of the Sphingomyelin in the of sphingomyelin and in with the and plasma of the of for the of a sphingomyelin and of sphingomyelin in SMS activity in and SMS SM Sphingomyelin synthase in liver and in sphingomyelin changes in the of SMS, of the of and with plasma SM levels the that no of for activity of a of sphingomyelin of a human cDNA sphingomyelin and in sphingomyelin are two isoforms of SMS SMS1 and in the the plasma of a of sphingomyelin we the adenovirus both SMS1 and SMS2 in the SMS and SM that both SMS1 and SMS2 significantly SM levels in and increased adenovirus and adenovirus vectors generated and SMS1 and SMS2 into the and of and were and with in were and into recombinant were and into were in and as in were AdV-SMS1 and and the were in adenovirus containing the LacZ To the of analysis a adenovirus that in were in of the recombinant adenovirus containing 2 × 1011 particles into the of day of the the were for were in containing and for and of plasma were and SMS2 mRNA with SMS1 and SMS2 mRNA levels were of total with and for for were with the of for of for for and for and of for were as control. for the were SMS1 SMS1 SMS2 SMS2 and with a and the of a for plasma and HDL-cholesterol plasma and HDL-SM and levels and of plasma sphingomyelin and and levels were as we of plasma and in and levels in total and were in of liver as and of plasma sphingomyelin and of and total cholesterol in of mRNA for the lipoprotein in containing the for human of lipoprotein B were a were the and were a SDS-PAGE were and were activity activity as Sphingomyelin synthase as a for in human the liver in a containing 1 and for and the for SMS activity and for 2 were in and with a and the of lipoprotein as sphingomyelin of plasma in apolipoprotein and and with of with of containing in for of the the for liver B and a of liver and the were analysis for B and a and a as a for the of and for vivo < < were with that with × or × the and for of the of and the of with plasma were are as P < the in vivo role of SMS1 and we AdV-SMS1 and AdV-SMS2 human SMS1 and SMS2 in AdV-LacZ as a control. of liver a increase of SMS1 mRNA and a increase of SMS2 mRNA levels in with AdV-SMS1 and compared with liver SMS activity the of SMS1 and SMS2 in AdV-SMS1 caused a increase in liver SMS AdV-SMS2 caused a compared with activity liver liver of and for 2 were in and of as in and are were with P < with are P < indicated in plasma analysis AdV-LacZ mice, and AdV-SMS2 AdV-LacZ showed a significant in HDL-SM (42% and 38%, respectively; P < and P < and HDL-cholesterol and 25%, respectively; P < and P < also a significant of (50% and 35%, respectively; P < and P < 0.05) and non-HDL-cholesterol and 61%, respectively; P < in and AdV-LacZ 7 7 7 SMS, sphingomyelin are with are < 0.05). in a of of plasma that HDL-SM and HDL-cholesterol were significantly decreased in AdV-SMS1 and AdV-SMS2 compared with AdV-LacZ of the apolipoprotein of total SDS-PAGE a significant increase of < 0.01) but plasma lipoprotein analysis of plasma a and with and of for the of cholesterol and analysis of < were as of the of for the of a sphingomyelin SDS-PAGE and the were and as of the of for the of a sphingomyelin are were with P < apolipoprotein of SM in the of that of lipoprotein SM lipoprotein a of the we that of with SM increase the enzyme sphingomyelin of plasma in apolipoprotein and and with To we in and significantly after treatment with also plasma activity the in a and no significant changes AdV-LacZ and AdV-SMS1 or AdV-SMS2 treatment that activity the of SM in of particles < were and of with of containing in for of the of are were with P < also and as well as and significant changes of for SM levels that both AdV-SMS1 and AdV-SMS2 SM but total changes in the in and AdV-LacZ are in a in and AdV-LacZ are in a that role in the of plasma into the liver of as a lipoprotein cholesterol and and cholesterol in B the adenovirus liver the of HDL-SM and HDL-cholesterol in AdV-SMS1 and AdV-SMS2 the of levels that AdV-SMS1 and AdV-SMS2 liver significantly levels liver and respectively; P < 0.01) that both a the controls. also and role in no significant analysis for B SDS-PAGE a of liver and the were analysis for apolipoprotein as in and are were with P < evaluate the of a in we in and and were with plasma of in AdV-SMS1 and AdV-SMS2 were and in < the of a of for and in in and AdV-LacZ < as < as and AdV-LacZ were with with and after of for and were the of and in plasma the of with plasma are P < as in a we for the that SMS1 and SMS2 significant of SMS1 and SMS2 mRNA of SMS of plasma non-HDL-SM and non-HDL-cholesterol of after of liver levels and and of plasma HDL-SM and HDL-cholesterol a of and and and plasma levels are both and the of SM the of a the enzyme of SM and SMS last enzyme of SM that the enzyme for of plasma and in of significantly plasma SM in of plasma and in of sphingomyelin in apolipoprotein that SMS also a in SM biosynthesis. with a SMS significantly decreased SMS in significantly decreased levels of SM a of the as well as SM in the and SMS activity It that SMS in sphingomyelin in the of sphingomyelin in It also that the activity of SMS of increased as in liver sphingomyelin in of sphingomyelin synthase of human Sphingomyelin a of levels of and sphingomyelin synthase for the and of sphingomyelin in the and the plasma that SMS activity in the of and that a and in we that both SMS1 and SMS2 in liver significant changes of SM and cholesterol in and that both SMS1 and SMS2 activity the of well that a of HDL-cholesterol lipoprotein and levels are in the but also in of as a lipoprotein cholesterol and and cholesterol in B and and role in we that AdV-SMS1 or AdV-SMS2 significantly but the of plasma HDL-SM and HDL-cholesterol levels SM in particles of of SM in and and and also with SM sphingomyelin of plasma in apolipoprotein and and with of SM in of total of in in with a of the we that after treatment with particles and were increased SM SMS1 and SMS2 significantly SM and in are two for we the changes of levels day we the and AdV-SMS1 and AdV-SMS2 the of SM the SM and plasma but the total of SM and cholesterol the of plasma in in the last that of the into of the plasma of SMS1 and SMS2 the in the of with plasma and of in of of the B in that plasma a for cholesterol and the of both and but are the of and of in of a of HDL-cholesterol and of non-HDL-cholesterol the indicated that SMS also no of levels in the we that both SMS1 and SMS2 plasma and also plasma we no changes of levels in and a that and for the and that with are in the for and and of in the of as and in the of the in of in and of in that SMS the of SMS in a in levels of and and we significant changes of liver levels of SMS1 and SMS2 and in SMS1 and SMS2 in a the increased plasma SM levels in sphingomyelin of plasma in apolipoprotein and and with in and and and of as well as in human sphingomyelin as a for of plasma sphingomyelin levels as a for Sphingomyelin (SM) of the in the of and of of human It for that plasma SM for sphingomyelin as a for and that in both in and in and in human in the of the in human in SM plasma containing human and of the in human SM levels in apolipoprotein are in sphingomyelin of plasma in apolipoprotein and and with and the increased in and the apolipoprotein SM levels are increased in in and and and and for the that SM decreased SM in the plasma and significantly decreased of of plasma and in of sphingomyelin in apolipoprotein that plasma SM a role in the of the of in with and cholesterol in the in in SM a of as for the of and for in of the into of the plasma of changes of SM lipoprotein metabolism, lipoprotein levels in the Sphingomyelin synthase the last enzyme in the SM that the the of SM and of the and of sphingomyelin the the that SM that SM synthase in the Sphingomyelin in liver the and of the Sphingomyelin in the of sphingomyelin and in with the and plasma of the of for the of a sphingomyelin and of sphingomyelin in SMS activity in and SMS SM Sphingomyelin synthase in liver and in sphingomyelin changes in the of SMS, of the of and with plasma SM levels the that no of for activity of a of sphingomyelin of a human cDNA sphingomyelin and in sphingomyelin are two isoforms of SMS SMS1 and in the the plasma of a of sphingomyelin we the adenovirus both SMS1 and SMS2 in the SMS and SM that both SMS1 and SMS2 significantly SM levels in and increased adenovirus and adenovirus vectors generated and SMS1 and SMS2 into the and of and were and with in were and into recombinant were and into were in and as in were AdV-SMS1 and and the were in adenovirus containing the LacZ To the of analysis a adenovirus that in were in of the recombinant adenovirus containing 2 × 1011 particles into the of day of the the were for were in containing and for and of plasma were and SMS2 mRNA with SMS1 and SMS2 mRNA levels were of total with and for for were with the of for of for for and for and of for were as control. for the were SMS1 SMS1 SMS2 SMS2 and with a and the of a for plasma and HDL-cholesterol plasma and HDL-SM and levels and of plasma sphingomyelin and and levels were as we of plasma and in and levels in total and were in of liver as and of plasma sphingomyelin and of and total cholesterol in of mRNA for the lipoprotein in containing the for human of lipoprotein B were a were the and were a SDS-PAGE were and were activity activity as Sphingomyelin synthase as a for in human the liver in a containing 1 and for and the for SMS activity and for 2 were in and with a and the of lipoprotein as sphingomyelin of plasma in apolipoprotein and and with of with of containing in for of the the for liver B and a of liver and the were analysis for B and a and a as a for the of and for vivo < < were with that with × or × the and for of the of and the of with plasma were are as P < adenovirus and adenovirus vectors generated and SMS1 and SMS2 into the and of and were and with in were and into recombinant were and into were in and as in were AdV-SMS1 and and the were in adenovirus containing the LacZ To the of analysis a adenovirus that in were in of the recombinant adenovirus containing 2 × 1011 particles into the of day of the the were for were in containing and for and of plasma were adenovirus vectors generated and SMS1 and SMS2 into the and of and were and with in were and into recombinant were and into were in and as in were AdV-SMS1 and and the were in adenovirus containing the LacZ To the of analysis a adenovirus that in were in of the recombinant adenovirus containing 2 × 1011 particles into the of day of the the were for were in containing and for and of plasma were SMS1 and SMS2 mRNA with SMS1 and SMS2 mRNA levels were of total with and for for were with the of for of for for and for and of for were as control. for the were SMS1 SMS1 SMS2 SMS2 and with a and the of with SMS1 and SMS2 mRNA levels were of total with and for for were with the of for of for for and for and of for were as control. for the were SMS1 SMS1 SMS2 SMS2 and with a and the of a for plasma and HDL-cholesterol plasma and HDL-SM and levels and of plasma sphingomyelin and a for plasma and HDL-cholesterol plasma and HDL-SM and levels and of plasma sphingomyelin and and levels were as we of plasma and in and levels in total and were in of liver as and of plasma sphingomyelin and of and total cholesterol in of mRNA for the lipoprotein in containing the for human of lipoprotein B and levels were as we of plasma and in and levels in total and were in of liver as and of plasma sphingomyelin and of and total cholesterol in of mRNA for the lipoprotein in containing the for human of lipoprotein B Lipoprotein were a were the and were a SDS-PAGE were and were Lipoprotein were a were the and were a SDS-PAGE were and were SMS activity activity as Sphingomyelin synthase as a for in human the liver in a containing 1 and for and the for SMS activity and for 2 were in and with a and the of SMS activity as Sphingomyelin synthase as a for in human the liver in a containing 1 and for and the for SMS activity and for 2 were in and with a and the of lipoprotein as sphingomyelin of plasma in apolipoprotein and and with of with of containing in for of the the Lipoprotein as sphingomyelin of plasma in apolipoprotein and and with of with of containing in for of the the for liver B and a of liver and the were analysis for B and a and a as a for the of and for SDS-PAGE a of liver and the were analysis for B and a and a as a for the of and for vivo < < were with that with × or × the and for of the of and the of with plasma < < were with that with × or × the and for of the of and the of with plasma were are as P < were are as P < the in vivo role of SMS1 and we AdV-SMS1 and AdV-SMS2 human SMS1 and SMS2 in AdV-LacZ as a control. of liver a increase of SMS1 mRNA and a increase of SMS2 mRNA levels in with AdV-SMS1 and compared with liver SMS activity the of SMS1 and SMS2 in AdV-SMS1 caused a increase in liver SMS AdV-SMS2 caused a compared with indicated in plasma analysis AdV-LacZ mice, and AdV-SMS2 AdV-LacZ showed a significant in HDL-SM (42% and 38%, respectively; P < and P < and HDL-cholesterol and 25%, respectively; P < and P < also a significant of (50% and 35%, respectively; P < and P < 0.05) and non-HDL-cholesterol and 61%, respectively; P < in and AdV-LacZ 7 7 7 SMS, sphingomyelin are with are < 0.05). in a of of plasma that HDL-SM and HDL-cholesterol were significantly decreased in AdV-SMS1 and AdV-SMS2 compared with AdV-LacZ of the apolipoprotein of total SDS-PAGE a significant increase of < 0.01) but plasma lipoprotein analysis of plasma a and with and of for the of cholesterol and analysis of < were as of the of for the of a sphingomyelin SDS-PAGE and the were and as of the of for the of a sphingomyelin are were with P < apolipoprotein of SM in the of that of lipoprotein SM lipoprotein a of the we that of with SM increase the enzyme sphingomyelin of plasma in apolipoprotein and and with To we in and significantly after treatment with also plasma activity the in a and no significant changes AdV-LacZ and AdV-SMS1 or AdV-SMS2 treatment that activity the of SM in of particles < were and of with of containing in for of the of are were with P < also and as well as and significant changes of for SM levels that both AdV-SMS1 and AdV-SMS2 SM but total changes in the in and AdV-LacZ are in a in and AdV-LacZ are in a that role in the of plasma into the liver of as a lipoprotein cholesterol and and cholesterol in B the adenovirus liver the of HDL-SM and HDL-cholesterol in AdV-SMS1 and AdV-SMS2 the of levels that AdV-SMS1 and AdV-SMS2 liver significantly levels liver and respectively; P < 0.01) that both a the controls. also and role in no significant analysis for B SDS-PAGE a of liver and the were analysis for apolipoprotein as in and are were with P < evaluate the of a in we in and and were with plasma of in AdV-SMS1 and AdV-SMS2 were and in < the of a of for and in in and AdV-LacZ < as < as and AdV-LacZ were with with and after of for and were the of and in plasma the of with plasma are P < as in a To the in vivo role of SMS1 and we AdV-SMS1 and AdV-SMS2 human SMS1 and SMS2 in AdV-LacZ as a control. of liver a increase of SMS1 mRNA and a increase of SMS2 mRNA levels in with AdV-SMS1 and compared with liver SMS activity the of SMS1 and SMS2 in AdV-SMS1 caused a increase in liver SMS AdV-SMS2 caused a compared with indicated in plasma analysis AdV-LacZ mice, and AdV-SMS2 AdV-LacZ showed a significant in HDL-SM (42% and 38%, respectively; P < and P < and HDL-cholesterol and 25%, respectively; P < and P < also a significant of (50% and 35%, respectively; P < and P < 0.05) and non-HDL-cholesterol and 61%, respectively; P < SMS, sphingomyelin are with are < 0.05). of of plasma that HDL-SM and HDL-cholesterol were significantly decreased in AdV-SMS1 and AdV-SMS2 compared with AdV-LacZ of the apolipoprotein of total SDS-PAGE a significant increase of < 0.01) but of SM in the of that of lipoprotein SM lipoprotein a of the we that of with SM increase the enzyme sphingomyelin of plasma in apolipoprotein and and with To we in and significantly after treatment with also plasma activity the in a and no significant changes AdV-LacZ and AdV-SMS1 or AdV-SMS2 treatment that activity the of SM in also and as well as and significant changes of for SM levels that both AdV-SMS1 and AdV-SMS2 SM but total changes in the are are that role in the of plasma into the liver of as a lipoprotein cholesterol and and cholesterol in B the adenovirus liver the of HDL-SM and HDL-cholesterol in AdV-SMS1 and AdV-SMS2 the of levels that AdV-SMS1 and AdV-SMS2 liver significantly levels liver and respectively; P < 0.01) that both a the controls. also and role in no significant To evaluate the of a in we in and and were with plasma of in AdV-SMS1 and AdV-SMS2 were and in < the of a of and AdV-LacZ were with with and after of for and were the of and in plasma the of with plasma are we for the that SMS1 and SMS2 significant of SMS1 and SMS2 mRNA of SMS of plasma non-HDL-SM and non-HDL-cholesterol of after of liver levels and and of plasma HDL-SM and HDL-cholesterol a of and and and plasma levels are both and the of SM the of a the enzyme of SM and SMS last enzyme of SM that the enzyme for of plasma and in of significantly plasma SM in of plasma and in of sphingomyelin in apolipoprotein that SMS also a in SM biosynthesis. with a SMS significantly decreased SMS in significantly decreased levels of SM a of the as well as SM in the and SMS activity It that SMS in sphingomyelin in the of sphingomyelin in It also that the activity of SMS of increased as in liver sphingomyelin in of sphingomyelin synthase of human Sphingomyelin a of levels of and sphingomyelin synthase for the and of sphingomyelin in the and the plasma that SMS activity in the of and that a and in we that both SMS1 and SMS2 in liver significant changes of SM and cholesterol in and that both SMS1 and SMS2 activity the of well that a of HDL-cholesterol lipoprotein and levels are in the but also in of as a lipoprotein cholesterol and and cholesterol in B and and role in we that AdV-SMS1 or AdV-SMS2 significantly but the of plasma HDL-SM and HDL-cholesterol levels SM in particles of of SM in and and and also with SM sphingomyelin of plasma in apolipoprotein and and with of SM in of total of in in with a of the we that after treatment with particles and were increased SM SMS1 and SMS2 significantly SM and in are two for we the changes of levels day we the and AdV-SMS1 and AdV-SMS2 the of SM the SM and plasma but the total of SM and cholesterol the of plasma in in the last that of the into of the plasma of SMS1 and SMS2 the in the of with plasma and of in of of the B in that plasma a for cholesterol and the of both and but are the of and of in of a of HDL-cholesterol and of non-HDL-cholesterol the indicated that SMS also no of levels in the we that both SMS1 and SMS2 plasma and also plasma we no changes of levels in and a that and for the and that with are in the for and and of in the of as and in the of the in of in and of in that SMS the of SMS in a in levels of and and we significant changes of liver levels of SMS1 and SMS2 and in SMS1 and SMS2 in a the increased plasma SM levels in sphingomyelin of plasma in apolipoprotein and and with in and and and of as well as in human sphingomyelin as a for of plasma sphingomyelin levels as a for we for the that SMS1 and SMS2 significant of SMS1 and SMS2 mRNA of SMS of plasma non-HDL-SM and non-HDL-cholesterol of after of liver levels and and of plasma HDL-SM and HDL-cholesterol SM a of and and and plasma levels are both and the of SM the of a the enzyme of SM and SMS last enzyme of SM that the enzyme for of plasma and in of significantly plasma SM in of plasma and in of sphingomyelin in apolipoprotein that SMS also a in SM biosynthesis. with a SMS significantly decreased SMS in significantly decreased levels of SM a of the as well as SM in the and SMS activity It that SMS in sphingomyelin in the of sphingomyelin in It also that the activity of SMS of increased as in liver sphingomyelin in of sphingomyelin synthase of human Sphingomyelin a of levels of and sphingomyelin synthase for the and of sphingomyelin in the and the plasma that SMS activity in the of and that a and in we that both SMS1 and SMS2 in liver significant changes of SM and cholesterol in and that both SMS1 and SMS2 activity the of It well that a of HDL-cholesterol lipoprotein and levels are in the but also in of as a lipoprotein cholesterol and and cholesterol in B and and role in we that AdV-SMS1 or AdV-SMS2 significantly but the of plasma HDL-SM and HDL-cholesterol levels SM in particles of of SM in and and and also with SM sphingomyelin of plasma in apolipoprotein and and with of SM in of total of in in with a of the we that after treatment with particles and were increased SM To SMS1 and SMS2 significantly SM and in are two for we the changes of levels day we the and AdV-SMS1 and AdV-SMS2 the of SM the SM and plasma but the total of SM and cholesterol the of plasma in in the last that of the into of the plasma of SMS1 and SMS2 the in the of with plasma and of in of of the B in that plasma a for cholesterol and the of both and but are the of and of in of a of HDL-cholesterol and of non-HDL-cholesterol the indicated that SMS also no of levels in the we that both SMS1 and SMS2 plasma and also plasma we no changes of levels in and a that and for the and that with are in the for and and of in the of as and in the of the in of in and of in that SMS the of SMS in a in levels of and and we significant changes of liver levels of SMS1 and SMS2 and in SMS1 and SMS2 in a the increased plasma SM levels in sphingomyelin of plasma in apolipoprotein and and with in and and and of as well as in human sphingomyelin as a for of plasma sphingomyelin levels as a for of
Dong et al. (Wed,) studied this question.
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