Diminished substrate‐mediated cardiac mitochondrial respiration and elevated autophagy in adult male offspring of gestational diabetic rats
Heart diseases are common in the offspring of diabetic mother (ODM). Defects in mitochondrial metabolism and autophagy may, in part, be responsible for the adverse structural and functional alterations in the heart. The principal objective of this study was to investigate cardiac mitochondrial respi...
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| Veröffentlicht in: | IUBMB life 2021-04, Vol.73 (4), p.676-689 |
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| creator | Raji, Sasikala Rajendran Nandini, Ravikumar Jayakumari Ashok, Sivasailam Anand, Chellappan Reghuvaran Vivek, Velayudhan Pillai Jayakumar, Karunakaran Harikrishnan, Vijayakumar Sreelatha Manjunatha, Shankarappa Gopala, Srinivas |
| description | Heart diseases are common in the offspring of diabetic mother (ODM). Defects in mitochondrial metabolism and autophagy may, in part, be responsible for the adverse structural and functional alterations in the heart. The principal objective of this study was to investigate cardiac mitochondrial respiration and autophagy in male and female offspring of diabetic pregnancy at two different developmental stages of life, weaning and adult. Male and female offspring of rats with streptozotocin‐induced gestational diabetes were used for the study and compared with offspring of control (non‐diabetic) mother (OCM) rats. High‐resolution respirometry was used to measure substrate‐mediated respiration in mitochondria isolated from ventricular tissues of ODM and OCM. Expression of proteins associated with autophagy and oxidative stress was examined by western blot analysis. Mitochondrial complex I and complex II respiration was significantly reduced in adult male ODM while it was unaltered or less affected in weaning male, adult and weaning female ODM. Elevated autophagy was observed in adult male but not in adult female ODM. Expression of oxidative stress markers was observed to be similar in all the groups. Altered cardiac mitochondrial respiration and autophagy were observed in adult male ODM compared to OCM, while the male and female offspring at weaning stage were less affected. The results of the study show that maternal hyperglycemia affects mitochondrial respiration and autophagy in the ODM heart, which may potentially be responsible for the cardiovascular complications observed in adult life. |
| doi_str_mv | 10.1002/iub.2449 |
| format | Article |
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Defects in mitochondrial metabolism and autophagy may, in part, be responsible for the adverse structural and functional alterations in the heart. The principal objective of this study was to investigate cardiac mitochondrial respiration and autophagy in male and female offspring of diabetic pregnancy at two different developmental stages of life, weaning and adult. Male and female offspring of rats with streptozotocin‐induced gestational diabetes were used for the study and compared with offspring of control (non‐diabetic) mother (OCM) rats. High‐resolution respirometry was used to measure substrate‐mediated respiration in mitochondria isolated from ventricular tissues of ODM and OCM. Expression of proteins associated with autophagy and oxidative stress was examined by western blot analysis. Mitochondrial complex I and complex II respiration was significantly reduced in adult male ODM while it was unaltered or less affected in weaning male, adult and weaning female ODM. Elevated autophagy was observed in adult male but not in adult female ODM. Expression of oxidative stress markers was observed to be similar in all the groups. Altered cardiac mitochondrial respiration and autophagy were observed in adult male ODM compared to OCM, while the male and female offspring at weaning stage were less affected. The results of the study show that maternal hyperglycemia affects mitochondrial respiration and autophagy in the ODM heart, which may potentially be responsible for the cardiovascular complications observed in adult life.</description><identifier>ISSN: 1521-6543</identifier><identifier>EISSN: 1521-6551</identifier><identifier>DOI: 10.1002/iub.2449</identifier><identifier>PMID: 33481330</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Animals ; Antioxidants - metabolism ; Autophagy ; Autophagy - physiology ; Blood Glucose - analysis ; Body Weight ; Coronary artery disease ; Developmental stages ; Diabetes ; Diabetes mellitus ; Diabetes Mellitus, Experimental ; Diabetes, Gestational ; Electron transport chain ; Enzymes - metabolism ; Female ; gestational diabetes ; heart ; Heart diseases ; Hyperglycemia ; Male ; Microtubule-Associated Proteins - metabolism ; Mitochondria ; Mitochondria, Heart - metabolism ; Mitochondria, Heart - pathology ; mitochondrial respiration ; NADH-ubiquinone oxidoreductase ; Offspring ; Oxidative stress ; Oxygen Consumption ; Phagocytosis ; Pregnancy ; Prenatal Exposure Delayed Effects ; Rats ; Rats, Wistar ; Respiration ; Streptozocin ; Structure-function relationships ; Ventricle ; Weaning</subject><ispartof>IUBMB life, 2021-04, Vol.73 (4), p.676-689</ispartof><rights>2021 International Union of Biochemistry and Molecular Biology</rights><rights>2021 International Union of Biochemistry and Molecular Biology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3839-9f4d070e48ece4e6fe6ee450fb3a2e2a49d666f83ebe1d71dc0f977d35e2a9a23</citedby><cites>FETCH-LOGICAL-c3839-9f4d070e48ece4e6fe6ee450fb3a2e2a49d666f83ebe1d71dc0f977d35e2a9a23</cites><orcidid>0000-0001-5885-6256</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fiub.2449$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fiub.2449$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,27901,27902,45550,45551,46384,46808</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33481330$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Raji, Sasikala Rajendran</creatorcontrib><creatorcontrib>Nandini, Ravikumar Jayakumari</creatorcontrib><creatorcontrib>Ashok, Sivasailam</creatorcontrib><creatorcontrib>Anand, Chellappan Reghuvaran</creatorcontrib><creatorcontrib>Vivek, Velayudhan Pillai</creatorcontrib><creatorcontrib>Jayakumar, Karunakaran</creatorcontrib><creatorcontrib>Harikrishnan, Vijayakumar Sreelatha</creatorcontrib><creatorcontrib>Manjunatha, Shankarappa</creatorcontrib><creatorcontrib>Gopala, Srinivas</creatorcontrib><title>Diminished substrate‐mediated cardiac mitochondrial respiration and elevated autophagy in adult male offspring of gestational diabetic rats</title><title>IUBMB life</title><addtitle>IUBMB Life</addtitle><description>Heart diseases are common in the offspring of diabetic mother (ODM). Defects in mitochondrial metabolism and autophagy may, in part, be responsible for the adverse structural and functional alterations in the heart. The principal objective of this study was to investigate cardiac mitochondrial respiration and autophagy in male and female offspring of diabetic pregnancy at two different developmental stages of life, weaning and adult. Male and female offspring of rats with streptozotocin‐induced gestational diabetes were used for the study and compared with offspring of control (non‐diabetic) mother (OCM) rats. High‐resolution respirometry was used to measure substrate‐mediated respiration in mitochondria isolated from ventricular tissues of ODM and OCM. Expression of proteins associated with autophagy and oxidative stress was examined by western blot analysis. Mitochondrial complex I and complex II respiration was significantly reduced in adult male ODM while it was unaltered or less affected in weaning male, adult and weaning female ODM. Elevated autophagy was observed in adult male but not in adult female ODM. Expression of oxidative stress markers was observed to be similar in all the groups. Altered cardiac mitochondrial respiration and autophagy were observed in adult male ODM compared to OCM, while the male and female offspring at weaning stage were less affected. The results of the study show that maternal hyperglycemia affects mitochondrial respiration and autophagy in the ODM heart, which may potentially be responsible for the cardiovascular complications observed in adult life.</description><subject>Animals</subject><subject>Antioxidants - metabolism</subject><subject>Autophagy</subject><subject>Autophagy - physiology</subject><subject>Blood Glucose - analysis</subject><subject>Body Weight</subject><subject>Coronary artery disease</subject><subject>Developmental stages</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus, Experimental</subject><subject>Diabetes, Gestational</subject><subject>Electron transport chain</subject><subject>Enzymes - metabolism</subject><subject>Female</subject><subject>gestational diabetes</subject><subject>heart</subject><subject>Heart diseases</subject><subject>Hyperglycemia</subject><subject>Male</subject><subject>Microtubule-Associated Proteins - metabolism</subject><subject>Mitochondria</subject><subject>Mitochondria, Heart - metabolism</subject><subject>Mitochondria, Heart - pathology</subject><subject>mitochondrial respiration</subject><subject>NADH-ubiquinone oxidoreductase</subject><subject>Offspring</subject><subject>Oxidative stress</subject><subject>Oxygen Consumption</subject><subject>Phagocytosis</subject><subject>Pregnancy</subject><subject>Prenatal Exposure Delayed Effects</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Respiration</subject><subject>Streptozocin</subject><subject>Structure-function relationships</subject><subject>Ventricle</subject><subject>Weaning</subject><issn>1521-6543</issn><issn>1521-6551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1KHTEUx0NRqtVCn0ACbroZm6_JnSzVfgmCG10PmeTk3sjM5JrMWO6uL1DoM_ZJerxaC4LZ5A_nlx_n5BDygbMTzpj4FOfuRChl3pB9Xgte6brmO89ZyT3yrpRbhmfBzFuyJ6VquJRsn_z6HIc4xrICT8vclSnbCf78_D2Aj5g8dTZjcnSIU3KrNPocbU8zlHVENKaR2tFT6OF-i9t5SuuVXW5oxIqf-4kOtgeaQijrHMclJrqEMm3fognlHUzRUbSVQ7IbbF_g_dN9QG6-frk-_15dXn27OD-9rJxspKlMUB4nAdWAAwU6gAZQNQudtAKEVcZrrUMjoQPuF9w7Fsxi4WWNRWOFPCAfH73rnO5m7KYdYnHQ93aENJdWqIZJVgujET1-gd6mOWPnSNXMiKYWWv8XupxKyRBaHHawedNy1j6sqMUVtQ8rQvToSTh3-MvP4L-dIFA9Aj9iD5tXRe3FzdlW-BeQ-p7S</recordid><startdate>202104</startdate><enddate>202104</enddate><creator>Raji, Sasikala Rajendran</creator><creator>Nandini, Ravikumar Jayakumari</creator><creator>Ashok, Sivasailam</creator><creator>Anand, Chellappan Reghuvaran</creator><creator>Vivek, Velayudhan Pillai</creator><creator>Jayakumar, Karunakaran</creator><creator>Harikrishnan, Vijayakumar Sreelatha</creator><creator>Manjunatha, Shankarappa</creator><creator>Gopala, Srinivas</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, 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>7X8</scope><orcidid>https://orcid.org/0000-0001-5885-6256</orcidid></search><sort><creationdate>202104</creationdate><title>Diminished substrate‐mediated cardiac mitochondrial respiration and elevated autophagy in adult male offspring of gestational diabetic rats</title><author>Raji, Sasikala Rajendran ; Nandini, Ravikumar Jayakumari ; Ashok, Sivasailam ; Anand, Chellappan Reghuvaran ; Vivek, Velayudhan Pillai ; Jayakumar, Karunakaran ; Harikrishnan, Vijayakumar Sreelatha ; Manjunatha, Shankarappa ; Gopala, Srinivas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3839-9f4d070e48ece4e6fe6ee450fb3a2e2a49d666f83ebe1d71dc0f977d35e2a9a23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Antioxidants - metabolism</topic><topic>Autophagy</topic><topic>Autophagy - physiology</topic><topic>Blood Glucose - analysis</topic><topic>Body Weight</topic><topic>Coronary artery disease</topic><topic>Developmental stages</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes Mellitus, Experimental</topic><topic>Diabetes, Gestational</topic><topic>Electron transport chain</topic><topic>Enzymes - metabolism</topic><topic>Female</topic><topic>gestational diabetes</topic><topic>heart</topic><topic>Heart diseases</topic><topic>Hyperglycemia</topic><topic>Male</topic><topic>Microtubule-Associated Proteins - metabolism</topic><topic>Mitochondria</topic><topic>Mitochondria, Heart - metabolism</topic><topic>Mitochondria, Heart - pathology</topic><topic>mitochondrial respiration</topic><topic>NADH-ubiquinone oxidoreductase</topic><topic>Offspring</topic><topic>Oxidative stress</topic><topic>Oxygen Consumption</topic><topic>Phagocytosis</topic><topic>Pregnancy</topic><topic>Prenatal Exposure Delayed Effects</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Respiration</topic><topic>Streptozocin</topic><topic>Structure-function relationships</topic><topic>Ventricle</topic><topic>Weaning</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Raji, Sasikala Rajendran</creatorcontrib><creatorcontrib>Nandini, Ravikumar Jayakumari</creatorcontrib><creatorcontrib>Ashok, Sivasailam</creatorcontrib><creatorcontrib>Anand, Chellappan Reghuvaran</creatorcontrib><creatorcontrib>Vivek, Velayudhan Pillai</creatorcontrib><creatorcontrib>Jayakumar, Karunakaran</creatorcontrib><creatorcontrib>Harikrishnan, Vijayakumar Sreelatha</creatorcontrib><creatorcontrib>Manjunatha, Shankarappa</creatorcontrib><creatorcontrib>Gopala, Srinivas</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>IUBMB life</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Raji, Sasikala Rajendran</au><au>Nandini, Ravikumar Jayakumari</au><au>Ashok, Sivasailam</au><au>Anand, Chellappan Reghuvaran</au><au>Vivek, Velayudhan Pillai</au><au>Jayakumar, Karunakaran</au><au>Harikrishnan, Vijayakumar Sreelatha</au><au>Manjunatha, Shankarappa</au><au>Gopala, Srinivas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Diminished substrate‐mediated cardiac mitochondrial respiration and elevated autophagy in adult male offspring of gestational diabetic rats</atitle><jtitle>IUBMB life</jtitle><addtitle>IUBMB Life</addtitle><date>2021-04</date><risdate>2021</risdate><volume>73</volume><issue>4</issue><spage>676</spage><epage>689</epage><pages>676-689</pages><issn>1521-6543</issn><eissn>1521-6551</eissn><abstract>Heart diseases are common in the offspring of diabetic mother (ODM). Defects in mitochondrial metabolism and autophagy may, in part, be responsible for the adverse structural and functional alterations in the heart. The principal objective of this study was to investigate cardiac mitochondrial respiration and autophagy in male and female offspring of diabetic pregnancy at two different developmental stages of life, weaning and adult. Male and female offspring of rats with streptozotocin‐induced gestational diabetes were used for the study and compared with offspring of control (non‐diabetic) mother (OCM) rats. High‐resolution respirometry was used to measure substrate‐mediated respiration in mitochondria isolated from ventricular tissues of ODM and OCM. Expression of proteins associated with autophagy and oxidative stress was examined by western blot analysis. Mitochondrial complex I and complex II respiration was significantly reduced in adult male ODM while it was unaltered or less affected in weaning male, adult and weaning female ODM. Elevated autophagy was observed in adult male but not in adult female ODM. Expression of oxidative stress markers was observed to be similar in all the groups. Altered cardiac mitochondrial respiration and autophagy were observed in adult male ODM compared to OCM, while the male and female offspring at weaning stage were less affected. The results of the study show that maternal hyperglycemia affects mitochondrial respiration and autophagy in the ODM heart, which may potentially be responsible for the cardiovascular complications observed in adult life.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>33481330</pmid><doi>10.1002/iub.2449</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0001-5885-6256</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antioxidants - metabolism Autophagy Autophagy - physiology Blood Glucose - analysis Body Weight Coronary artery disease Developmental stages Diabetes Diabetes mellitus Diabetes Mellitus, Experimental Diabetes, Gestational Electron transport chain Enzymes - metabolism Female gestational diabetes heart Heart diseases Hyperglycemia Male Microtubule-Associated Proteins - metabolism Mitochondria Mitochondria, Heart - metabolism Mitochondria, Heart - pathology mitochondrial respiration NADH-ubiquinone oxidoreductase Offspring Oxidative stress Oxygen Consumption Phagocytosis Pregnancy Prenatal Exposure Delayed Effects Rats Rats, Wistar Respiration Streptozocin Structure-function relationships Ventricle Weaning |
| title | Diminished substrate‐mediated cardiac mitochondrial respiration and elevated autophagy in adult male offspring of gestational diabetic rats |
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