High glucose-induced replicative senescence: point of no return and effect of telomerase
Primary human cells enter senescence after a characteristic number of population doublings (PDs). In the current study, human skin fibroblasts were propagated in culture under 5.5 mM glucose (normoglycemia); addition of 16.5 mM d-glucose to a concentration of 22 mM (hyperglycemia); and addition of 1...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2002-08, Vol.296 (1), p.93-101 |
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| container_title | Biochemical and biophysical research communications |
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| creator | Blazer, Shraga Khankin, Eli Segev, Yardena Ofir, Rachel Yalon-Hacohen, Michal Kra-Oz, Zipora Gottfried, Yossi Larisch, Sarit Skorecki, Karl L |
| description | Primary human cells enter senescence after a characteristic number of population doublings (PDs). In the current study, human skin fibroblasts were propagated in culture under 5.5
mM glucose (normoglycemia); addition of 16.5
mM
d-glucose to a concentration of 22
mM (hyperglycemia); and addition of 16.5
mM
l-glucose (osmotic control). Hyperglycemia induced premature replicative senescence after 44.42±1.5 PDs compared to 57.9±3.83 PDs under normoglycemia (
p |
| doi_str_mv | 10.1016/S0006-291X(02)00818-5 |
| format | Article |
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mM glucose (normoglycemia); addition of 16.5
mM
d-glucose to a concentration of 22
mM (hyperglycemia); and addition of 16.5
mM
l-glucose (osmotic control). Hyperglycemia induced premature replicative senescence after 44.42±1.5 PDs compared to 57.9±3.83 PDs under normoglycemia (
p<0.0001).
l-Glucose had no effect, suggesting that the effect of hyperglycemia was not attributed to hyperosmolarity. Activated caspase-3 measurement showed a significantly higher percentage of apoptotic cells in high glucose medium. Telomerase overexpression circumvented the effects of hyperglycemia on replicative capacity and apoptosis. The “point of no return,” beyond which hyperglycemia resulted in irreversible progression to premature replicative senescence, occurred after exposure to hyperglycemia for as few as 20 PDs. These results may provide a biochemical basis for the relationship between hyperglycemia and those complications of diabetes, which are reminiscent of accelerated senescence.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/S0006-291X(02)00818-5</identifier><identifier>PMID: 12147232</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Apoptosis ; Cell Division - drug effects ; Cellular Senescence - drug effects ; Culture Media ; Diabetes ; Fibroblasts - cytology ; Fibroblasts - drug effects ; Glucose - pharmacology ; Humans ; Hyperglycemia ; Hyperosmolality ; Replicative arrest ; Senescence ; Skin - cytology ; Skin - drug effects ; Skin fibroblasts ; Telomerase ; Telomerase - physiology</subject><ispartof>Biochemical and biophysical research communications, 2002-08, Vol.296 (1), p.93-101</ispartof><rights>2002 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c444t-a3e05c09b3ea451edbbde1ddff8c4adcc942d755ad5facfd4d0f6140c7eb27703</citedby><cites>FETCH-LOGICAL-c444t-a3e05c09b3ea451edbbde1ddff8c4adcc942d755ad5facfd4d0f6140c7eb27703</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0006-291X(02)00818-5$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12147232$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Blazer, Shraga</creatorcontrib><creatorcontrib>Khankin, Eli</creatorcontrib><creatorcontrib>Segev, Yardena</creatorcontrib><creatorcontrib>Ofir, Rachel</creatorcontrib><creatorcontrib>Yalon-Hacohen, Michal</creatorcontrib><creatorcontrib>Kra-Oz, Zipora</creatorcontrib><creatorcontrib>Gottfried, Yossi</creatorcontrib><creatorcontrib>Larisch, Sarit</creatorcontrib><creatorcontrib>Skorecki, Karl L</creatorcontrib><title>High glucose-induced replicative senescence: point of no return and effect of telomerase</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Primary human cells enter senescence after a characteristic number of population doublings (PDs). In the current study, human skin fibroblasts were propagated in culture under 5.5
mM glucose (normoglycemia); addition of 16.5
mM
d-glucose to a concentration of 22
mM (hyperglycemia); and addition of 16.5
mM
l-glucose (osmotic control). Hyperglycemia induced premature replicative senescence after 44.42±1.5 PDs compared to 57.9±3.83 PDs under normoglycemia (
p<0.0001).
l-Glucose had no effect, suggesting that the effect of hyperglycemia was not attributed to hyperosmolarity. Activated caspase-3 measurement showed a significantly higher percentage of apoptotic cells in high glucose medium. Telomerase overexpression circumvented the effects of hyperglycemia on replicative capacity and apoptosis. The “point of no return,” beyond which hyperglycemia resulted in irreversible progression to premature replicative senescence, occurred after exposure to hyperglycemia for as few as 20 PDs. These results may provide a biochemical basis for the relationship between hyperglycemia and those complications of diabetes, which are reminiscent of accelerated senescence.</description><subject>Apoptosis</subject><subject>Cell Division - drug effects</subject><subject>Cellular Senescence - drug effects</subject><subject>Culture Media</subject><subject>Diabetes</subject><subject>Fibroblasts - cytology</subject><subject>Fibroblasts - drug effects</subject><subject>Glucose - pharmacology</subject><subject>Humans</subject><subject>Hyperglycemia</subject><subject>Hyperosmolality</subject><subject>Replicative arrest</subject><subject>Senescence</subject><subject>Skin - cytology</subject><subject>Skin - drug effects</subject><subject>Skin fibroblasts</subject><subject>Telomerase</subject><subject>Telomerase - physiology</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMFO3DAQhi1EBQv0EVrlhMohZcaxkw2XqkLAIq3UA1Tam-XYY-oqGy92gtS3b7K7guOeRhp9__yjj7EvCN8RsLx-AoAy5zWuvgG_ApjjPJdHbIZQQ84RxDGbvSOn7CylvwCIoqxP2ClyFBUv-IytFv7lT_bSDiYkyn1nB0M2i7RpvdG9f6MsUUfJUGfoJtsE3_VZcFkXRqYfYpfpzmbkHJntvqc2rCnqRBfsk9Ntos_7ec5-39893y7y5a-Hx9ufy9wIIfpcFwTSQN0UpIVEsk1jCa11bm6EtsbUgttKSm2l08ZZYcGVKMBU1PCqguKcXe7ubmJ4HSj1au3Hd9tWdxSGpCqsZSHk_CCIdVHLEuQIyh1oYkgpklOb6Nc6_lMIanKvtu7VJFYBV1v3asp93RcMzZrsR2ovewR-7AAafbx5iioZP4m1Po7-lA3-QMV_AzqVwA</recordid><startdate>20020809</startdate><enddate>20020809</enddate><creator>Blazer, Shraga</creator><creator>Khankin, Eli</creator><creator>Segev, Yardena</creator><creator>Ofir, Rachel</creator><creator>Yalon-Hacohen, Michal</creator><creator>Kra-Oz, Zipora</creator><creator>Gottfried, Yossi</creator><creator>Larisch, Sarit</creator><creator>Skorecki, Karl L</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>7X8</scope></search><sort><creationdate>20020809</creationdate><title>High glucose-induced replicative senescence: point of no return and effect of telomerase</title><author>Blazer, Shraga ; Khankin, Eli ; Segev, Yardena ; Ofir, Rachel ; Yalon-Hacohen, Michal ; Kra-Oz, Zipora ; Gottfried, Yossi ; Larisch, Sarit ; Skorecki, Karl L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c444t-a3e05c09b3ea451edbbde1ddff8c4adcc942d755ad5facfd4d0f6140c7eb27703</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Apoptosis</topic><topic>Cell Division - drug effects</topic><topic>Cellular Senescence - drug effects</topic><topic>Culture Media</topic><topic>Diabetes</topic><topic>Fibroblasts - cytology</topic><topic>Fibroblasts - drug effects</topic><topic>Glucose - pharmacology</topic><topic>Humans</topic><topic>Hyperglycemia</topic><topic>Hyperosmolality</topic><topic>Replicative arrest</topic><topic>Senescence</topic><topic>Skin - cytology</topic><topic>Skin - drug effects</topic><topic>Skin fibroblasts</topic><topic>Telomerase</topic><topic>Telomerase - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Blazer, Shraga</creatorcontrib><creatorcontrib>Khankin, Eli</creatorcontrib><creatorcontrib>Segev, Yardena</creatorcontrib><creatorcontrib>Ofir, Rachel</creatorcontrib><creatorcontrib>Yalon-Hacohen, Michal</creatorcontrib><creatorcontrib>Kra-Oz, Zipora</creatorcontrib><creatorcontrib>Gottfried, Yossi</creatorcontrib><creatorcontrib>Larisch, Sarit</creatorcontrib><creatorcontrib>Skorecki, Karl L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Blazer, Shraga</au><au>Khankin, Eli</au><au>Segev, Yardena</au><au>Ofir, Rachel</au><au>Yalon-Hacohen, Michal</au><au>Kra-Oz, Zipora</au><au>Gottfried, Yossi</au><au>Larisch, Sarit</au><au>Skorecki, Karl L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High glucose-induced replicative senescence: point of no return and effect of telomerase</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2002-08-09</date><risdate>2002</risdate><volume>296</volume><issue>1</issue><spage>93</spage><epage>101</epage><pages>93-101</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Primary human cells enter senescence after a characteristic number of population doublings (PDs). In the current study, human skin fibroblasts were propagated in culture under 5.5
mM glucose (normoglycemia); addition of 16.5
mM
d-glucose to a concentration of 22
mM (hyperglycemia); and addition of 16.5
mM
l-glucose (osmotic control). Hyperglycemia induced premature replicative senescence after 44.42±1.5 PDs compared to 57.9±3.83 PDs under normoglycemia (
p<0.0001).
l-Glucose had no effect, suggesting that the effect of hyperglycemia was not attributed to hyperosmolarity. Activated caspase-3 measurement showed a significantly higher percentage of apoptotic cells in high glucose medium. Telomerase overexpression circumvented the effects of hyperglycemia on replicative capacity and apoptosis. The “point of no return,” beyond which hyperglycemia resulted in irreversible progression to premature replicative senescence, occurred after exposure to hyperglycemia for as few as 20 PDs. These results may provide a biochemical basis for the relationship between hyperglycemia and those complications of diabetes, which are reminiscent of accelerated senescence.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>12147232</pmid><doi>10.1016/S0006-291X(02)00818-5</doi><tpages>9</tpages></addata></record> |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Apoptosis Cell Division - drug effects Cellular Senescence - drug effects Culture Media Diabetes Fibroblasts - cytology Fibroblasts - drug effects Glucose - pharmacology Humans Hyperglycemia Hyperosmolality Replicative arrest Senescence Skin - cytology Skin - drug effects Skin fibroblasts Telomerase Telomerase - physiology |
| title | High glucose-induced replicative senescence: point of no return and effect of telomerase |
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