Latanoprost rescues retinal neuro-glial cells from apoptosis by inhibiting caspase-3, which is mediated by p44/p42 mitogen-activated protein kinase
The purpose of this study was to investigate whether latanoprost, a prostaglandin F2α analogue, has a direct anti-apoptotic effect both in retinal neuro-glial cells in culture and in diabetic retina. R28 cells, immortalized retinal neuroglial progenitor cells, were induced apoptosis by 24h serum dep...
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| Veröffentlicht in: | Experimental eye research 2006-11, Vol.83 (5), p.1108-1117 |
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| creator | Nakanishi, Yoriko Nakamura, Makoto Mukuno, Hirokazu Kanamori, Akiyasu Seigel, Gail M. Negi, Akira |
| description | The purpose of this study was to investigate whether latanoprost, a prostaglandin F2α analogue, has a direct anti-apoptotic effect both in retinal neuro-glial cells in culture and in diabetic retina. R28 cells, immortalized retinal neuroglial progenitor cells, were induced apoptosis by 24h serum deprivation. Serum withdrawal made up to 15% of R28 cells pyknotic and activated caspase-3 immunoreactive, and latanoprost acid suppressed apoptosis with dose dependency at an optimum concentration of 1.0μM (P |
| doi_str_mv | 10.1016/j.exer.2006.05.018 |
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R28 cells, immortalized retinal neuroglial progenitor cells, were induced apoptosis by 24h serum deprivation. Serum withdrawal made up to 15% of R28 cells pyknotic and activated caspase-3 immunoreactive, and latanoprost acid suppressed apoptosis with dose dependency at an optimum concentration of 1.0μM (P<0.001). UO126, a mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase kinase (MEK) 1 and 2 inhibitor reversed this effect. Streptozotocin induced one- or three-month diabetic rats received balanced-salt-solution (BSS) in the left eye and latanoprost eye drops in the right for 5days. Retinal wholemount was subjected to terminal dUTP nick end labeling (TUNEL) staining, whereas eyeballs were enucleated for cleaved caspase-3 immunofluorescence. Retinal homogenates were probed for phospho- or total p44/p42 MAPK and Akt. One- and three-month diabetic retina had 30.2±15.3 and 23.6±9.0 TUNEL positive cells per 0.5cm2, respectively, whereas control retina had few TUNEL positive cells. Latanoprost instillation significantly reduced these cells (10.0±3.1 and 11.3±3.1 cells per 0.5cm2 for 1M and 3M, respectively, P<0.01), whereas BSS did not. Latanoprost also significantly reduced cleaved caspase-3 immunoreactive cells in ganglion cell and inner nuclear layers (P<0.05). Latanoprost increased phosphorylated to total protein ratio of p44/p42 MAPK (P<0.05), but not of Akt. Taken together, the present findings suggest that latanoprost rescues retinal neurons and/or glial cells from apoptosis, which is probably mediated by p44/p42 MAPK through caspase-3 inhibition.</description><identifier>ISSN: 0014-4835</identifier><identifier>EISSN: 1096-0007</identifier><identifier>DOI: 10.1016/j.exer.2006.05.018</identifier><identifier>PMID: 16839545</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; apoptosis ; Apoptosis - drug effects ; Caspase Inhibitors ; Cell Line ; Diabetes Mellitus, Experimental - physiopathology ; diabetic retinopathy ; Diabetic Retinopathy - physiopathology ; Dose-Response Relationship, Drug ; Enzyme Inhibitors - pharmacology ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Immunohistochemistry - methods ; latanoprost ; Male ; mitogen-activated protein kinase ; Mitogen-Activated Protein Kinase 1 - metabolism ; Mitogen-Activated Protein Kinase 3 - metabolism ; Neuroglia - drug effects ; Neuroglia - physiology ; Neuroprotective Agents - pharmacology ; Ophthalmic Solutions - pharmacology ; Prostaglandins F, Synthetic - pharmacology ; Rats ; Rats, Sprague-Dawley ; Retina - cytology ; Retina - drug effects ; Retinal Ganglion Cells - drug effects ; Retinal Ganglion Cells - physiology ; retinal neurodegeneration ; Stem Cells - drug effects ; Stem Cells - physiology</subject><ispartof>Experimental eye research, 2006-11, Vol.83 (5), p.1108-1117</ispartof><rights>2006 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c508t-a273893ae8e93bbb1e57be62bec73448bb354086d3f2556735f9968f120cee723</citedby><cites>FETCH-LOGICAL-c508t-a273893ae8e93bbb1e57be62bec73448bb354086d3f2556735f9968f120cee723</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0014483506002727$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16839545$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nakanishi, Yoriko</creatorcontrib><creatorcontrib>Nakamura, Makoto</creatorcontrib><creatorcontrib>Mukuno, Hirokazu</creatorcontrib><creatorcontrib>Kanamori, Akiyasu</creatorcontrib><creatorcontrib>Seigel, Gail M.</creatorcontrib><creatorcontrib>Negi, Akira</creatorcontrib><title>Latanoprost rescues retinal neuro-glial cells from apoptosis by inhibiting caspase-3, which is mediated by p44/p42 mitogen-activated protein kinase</title><title>Experimental eye research</title><addtitle>Exp Eye Res</addtitle><description>The purpose of this study was to investigate whether latanoprost, a prostaglandin F2α analogue, has a direct anti-apoptotic effect both in retinal neuro-glial cells in culture and in diabetic retina. R28 cells, immortalized retinal neuroglial progenitor cells, were induced apoptosis by 24h serum deprivation. Serum withdrawal made up to 15% of R28 cells pyknotic and activated caspase-3 immunoreactive, and latanoprost acid suppressed apoptosis with dose dependency at an optimum concentration of 1.0μM (P<0.001). UO126, a mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase kinase (MEK) 1 and 2 inhibitor reversed this effect. Streptozotocin induced one- or three-month diabetic rats received balanced-salt-solution (BSS) in the left eye and latanoprost eye drops in the right for 5days. Retinal wholemount was subjected to terminal dUTP nick end labeling (TUNEL) staining, whereas eyeballs were enucleated for cleaved caspase-3 immunofluorescence. Retinal homogenates were probed for phospho- or total p44/p42 MAPK and Akt. One- and three-month diabetic retina had 30.2±15.3 and 23.6±9.0 TUNEL positive cells per 0.5cm2, respectively, whereas control retina had few TUNEL positive cells. Latanoprost instillation significantly reduced these cells (10.0±3.1 and 11.3±3.1 cells per 0.5cm2 for 1M and 3M, respectively, P<0.01), whereas BSS did not. Latanoprost also significantly reduced cleaved caspase-3 immunoreactive cells in ganglion cell and inner nuclear layers (P<0.05). Latanoprost increased phosphorylated to total protein ratio of p44/p42 MAPK (P<0.05), but not of Akt. Taken together, the present findings suggest that latanoprost rescues retinal neurons and/or glial cells from apoptosis, which is probably mediated by p44/p42 MAPK through caspase-3 inhibition.</description><subject>Animals</subject><subject>apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Caspase Inhibitors</subject><subject>Cell Line</subject><subject>Diabetes Mellitus, Experimental - physiopathology</subject><subject>diabetic retinopathy</subject><subject>Diabetic Retinopathy - physiopathology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>Immunohistochemistry - methods</subject><subject>latanoprost</subject><subject>Male</subject><subject>mitogen-activated protein kinase</subject><subject>Mitogen-Activated Protein Kinase 1 - metabolism</subject><subject>Mitogen-Activated Protein Kinase 3 - metabolism</subject><subject>Neuroglia - drug effects</subject><subject>Neuroglia - physiology</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Ophthalmic Solutions - pharmacology</subject><subject>Prostaglandins F, Synthetic - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Retina - cytology</subject><subject>Retina - drug effects</subject><subject>Retinal Ganglion Cells - drug effects</subject><subject>Retinal Ganglion Cells - physiology</subject><subject>retinal neurodegeneration</subject><subject>Stem Cells - drug effects</subject><subject>Stem Cells - physiology</subject><issn>0014-4835</issn><issn>1096-0007</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc-O0zAQxi0EYrsLL8AB-cSJZO34byQuaAULUiUucLZsd9K6JHGw3YV9Dl4Yh1bixmksz2_m03wfQq8oaSmh8vbYwi9IbUeIbIloCdVP0IaSXjaEEPUUbQihvOGaiSt0nfOx_jKu-HN0RaVmveBig35vbbFzXFLMBSfI_gS51hJmO-IZTik2-zHUt4dxzHhIccJ2iUuJOWTsHnGYD8GFyu-xt3mxGRr2Fv88BH_AlZhgF2yB3YounN8uvMNTKHEPc2N9CQ9_m1W-QJjx9yqb4QV6Ntgxw8tLvUHfPn74evep2X65_3z3ftt4QXRpbKeY7pkFDT1zzlEQyoHsHHjFONfOMcGJljs2dEJIxcTQ91IPtCMeQHXsBr05763yP-rdxUwhr3faGeIpG6m1UpyICnZn0FebcoLBLClMNj0aSswahTmaNQqzRmGIMDWKOvT6sv3kqgv_Ri7eV-DdGYB640Oo49kHmH11LIEvZhfD__b_AeZLnLw</recordid><startdate>200611</startdate><enddate>200611</enddate><creator>Nakanishi, Yoriko</creator><creator>Nakamura, Makoto</creator><creator>Mukuno, Hirokazu</creator><creator>Kanamori, Akiyasu</creator><creator>Seigel, Gail M.</creator><creator>Negi, Akira</creator><general>Elsevier Ltd</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>7X8</scope></search><sort><creationdate>200611</creationdate><title>Latanoprost rescues retinal neuro-glial cells from apoptosis by inhibiting caspase-3, which is mediated by p44/p42 mitogen-activated protein kinase</title><author>Nakanishi, Yoriko ; Nakamura, Makoto ; Mukuno, Hirokazu ; Kanamori, Akiyasu ; Seigel, Gail M. ; Negi, Akira</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c508t-a273893ae8e93bbb1e57be62bec73448bb354086d3f2556735f9968f120cee723</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Caspase Inhibitors</topic><topic>Cell Line</topic><topic>Diabetes Mellitus, Experimental - physiopathology</topic><topic>diabetic retinopathy</topic><topic>Diabetic Retinopathy - physiopathology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>Immunohistochemistry - methods</topic><topic>latanoprost</topic><topic>Male</topic><topic>mitogen-activated protein kinase</topic><topic>Mitogen-Activated Protein Kinase 1 - metabolism</topic><topic>Mitogen-Activated Protein Kinase 3 - metabolism</topic><topic>Neuroglia - drug effects</topic><topic>Neuroglia - physiology</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Ophthalmic Solutions - pharmacology</topic><topic>Prostaglandins F, Synthetic - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Retina - cytology</topic><topic>Retina - drug effects</topic><topic>Retinal Ganglion Cells - drug effects</topic><topic>Retinal Ganglion Cells - physiology</topic><topic>retinal neurodegeneration</topic><topic>Stem Cells - drug effects</topic><topic>Stem Cells - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nakanishi, Yoriko</creatorcontrib><creatorcontrib>Nakamura, Makoto</creatorcontrib><creatorcontrib>Mukuno, Hirokazu</creatorcontrib><creatorcontrib>Kanamori, Akiyasu</creatorcontrib><creatorcontrib>Seigel, Gail M.</creatorcontrib><creatorcontrib>Negi, Akira</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental eye research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nakanishi, Yoriko</au><au>Nakamura, Makoto</au><au>Mukuno, Hirokazu</au><au>Kanamori, Akiyasu</au><au>Seigel, Gail M.</au><au>Negi, Akira</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Latanoprost rescues retinal neuro-glial cells from apoptosis by inhibiting caspase-3, which is mediated by p44/p42 mitogen-activated protein kinase</atitle><jtitle>Experimental eye research</jtitle><addtitle>Exp Eye Res</addtitle><date>2006-11</date><risdate>2006</risdate><volume>83</volume><issue>5</issue><spage>1108</spage><epage>1117</epage><pages>1108-1117</pages><issn>0014-4835</issn><eissn>1096-0007</eissn><abstract>The purpose of this study was to investigate whether latanoprost, a prostaglandin F2α analogue, has a direct anti-apoptotic effect both in retinal neuro-glial cells in culture and in diabetic retina. R28 cells, immortalized retinal neuroglial progenitor cells, were induced apoptosis by 24h serum deprivation. Serum withdrawal made up to 15% of R28 cells pyknotic and activated caspase-3 immunoreactive, and latanoprost acid suppressed apoptosis with dose dependency at an optimum concentration of 1.0μM (P<0.001). UO126, a mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase kinase (MEK) 1 and 2 inhibitor reversed this effect. Streptozotocin induced one- or three-month diabetic rats received balanced-salt-solution (BSS) in the left eye and latanoprost eye drops in the right for 5days. Retinal wholemount was subjected to terminal dUTP nick end labeling (TUNEL) staining, whereas eyeballs were enucleated for cleaved caspase-3 immunofluorescence. Retinal homogenates were probed for phospho- or total p44/p42 MAPK and Akt. One- and three-month diabetic retina had 30.2±15.3 and 23.6±9.0 TUNEL positive cells per 0.5cm2, respectively, whereas control retina had few TUNEL positive cells. Latanoprost instillation significantly reduced these cells (10.0±3.1 and 11.3±3.1 cells per 0.5cm2 for 1M and 3M, respectively, P<0.01), whereas BSS did not. Latanoprost also significantly reduced cleaved caspase-3 immunoreactive cells in ganglion cell and inner nuclear layers (P<0.05). Latanoprost increased phosphorylated to total protein ratio of p44/p42 MAPK (P<0.05), but not of Akt. Taken together, the present findings suggest that latanoprost rescues retinal neurons and/or glial cells from apoptosis, which is probably mediated by p44/p42 MAPK through caspase-3 inhibition.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>16839545</pmid><doi>10.1016/j.exer.2006.05.018</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals apoptosis Apoptosis - drug effects Caspase Inhibitors Cell Line Diabetes Mellitus, Experimental - physiopathology diabetic retinopathy Diabetic Retinopathy - physiopathology Dose-Response Relationship, Drug Enzyme Inhibitors - pharmacology Extracellular Signal-Regulated MAP Kinases - metabolism Immunohistochemistry - methods latanoprost Male mitogen-activated protein kinase Mitogen-Activated Protein Kinase 1 - metabolism Mitogen-Activated Protein Kinase 3 - metabolism Neuroglia - drug effects Neuroglia - physiology Neuroprotective Agents - pharmacology Ophthalmic Solutions - pharmacology Prostaglandins F, Synthetic - pharmacology Rats Rats, Sprague-Dawley Retina - cytology Retina - drug effects Retinal Ganglion Cells - drug effects Retinal Ganglion Cells - physiology retinal neurodegeneration Stem Cells - drug effects Stem Cells - physiology |
| title | Latanoprost rescues retinal neuro-glial cells from apoptosis by inhibiting caspase-3, which is mediated by p44/p42 mitogen-activated protein kinase |
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