2026-05-21T23:03:36Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/173942024-09-21T09:45:13Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Sánchez-Ramos, Cristina
author
Prieto, Ignacio
author
Tierrez, Alberto
author
Laso, Javier
author
Valdecantos, M Pilar
author
Bartrons, Ramon
author
Roselló-Catafau, Joan
author
Monsalve, María
2024-01-31T13:59:00Z
2024-01-31T13:59:00Z
2017-12-01
Antioxid Redox Signal. 2017 Dec 1;27(16):1332-1346.
10.1089/ars.2016.6836
1557-7716
Antioxidants & redox signaling
28269997
http://hdl.handle.net/20.500.12105/17394
AIMS
Liver steatosis is associated with mitochondrial dysfunction and elevated reactive oxygen species (ROS) levels together with enhanced sensitivity to ischemia-reperfusion (IR) injury and limited response to preconditioning protocols. Here, we sought to determine whether the downregulation in the steatotic liver of peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α), a master regulator of mitochondrial metabolism and ROS that is known to play a role in liver metabolic control, could be responsible for the sensitivity of the steatotic liver to ischemic damage.
RESULTS
PGC-1α was induced in normal liver after exposure to an IR protocol, which was concomitant with an increase in the levels of antioxidant proteins. By contrast, its induction was severely blunted in the steatotic liver, resulting in a modest induction of antioxidant proteins. Livers of PGC-1α-/- mice on a chow diet were normal, but they exhibited an enhanced sensitivity to IR injury and also a lack of response to ischemic preconditioning (IPC), a phenotype that recapitulated the features of the steatotic liver in terms of liver damage, although the inflammatory response differed between both models. Utilizing an in vitro model of IPC, we found that PGC-1α expression was downregulated in hepatic cells cultured at 1% O2; whereas it was induced after reoxygenation (3% O2), and it was responsible for the recovery of antioxidant gene expression after the ischemic period. Innovation & Conclusion: PGC-1α plays an important role in the protection against IR injury in the liver, which is likely associated with its capacity to induce antioxidant gene expression. Antioxid. Redox Signal. 27, 1332-1346.
eng
PGC-1α Downregulation in Steatotic Liver Enhances Ischemia-Reperfusion Injury and Impairs Ischemic Preconditioning.
journal article
TElDRU5DSUEgREUgRElTVFJJQlVDScOTTiBOTyBFWENMVVNJVkEKCkFjZXB0YW5kbyBlc3RhIGxpY2VuY2lhLCBVc3RlZCAoZWwgYXV0b3IvZXMgbyBlbCBwcm9waWV0YXJpby9zIGRlIGxvcyBkZXJlY2hvcyBkZSAKYXV0b3IpIGNvbmNlZGUgYSBSRVBJU0FMVUQgZWwgZGVyZWNobyBubyBleGNsdXNpdm8gZGUgcmVwcm9kdWNpciwgY29udmVydGlyLCB5L28gCmRpc3RyaWJ1aXIgc3UgZG9jdW1lbnRvIChpbmNsdXllbmRvIHN1IHJlc3VtZW4pIGEgbml2ZWwgbXVuZGlhbCBlbiBmb3JtYXRvIGRpZ2l0YWwsIAppbmNsdXllbmRvLCBhdWRpbyB5IHbDrWRlbywgYSB0cmF2w6lzIGRlIHN1IHJlcG9zaXRvcmlvIGluc3RpdHVjaW9uYWwuCgpVc3RlZCBhY2VwdGEgcXVlIFJFUElTQUxVRCBwdWVkZSwgc2luIGFsdGVyYXIgc3UgY29udGVuaWRvLCBjb252ZXJ0aXIgc3UgZG9jdW1lbnRvIAphIGN1YWxxdWllciBvdHJvIGZvcm1hdG8gZGlnaXRhbCBkZSBkYXRvcywgYXVkaW8geSB2aWRlbywgY29uIGVsIHByb3DDs3NpdG8gZGUgcXVlIApwdWVkYSBzZXIgYWxvamFkbyBlbiBlbCByZXBvc2l0b3Jpby4gCgpVc3RlZCBlc3TDoSBkZSBhY3VlcmRvIGNvbiBxdWUgUkVQSVNBTFVEIHB1ZWRhIGNvbnNlcnZhciBtw6FzIGRlIHVuYSBjb3BpYSBkZSBlc3RlIApkb2N1bWVudG8gcGFyYSBhc2VndXJhciBzdSBzZWd1cmlkYWQsIHByZXNlcnZhY2nDs24geSBhY2Nlc28uCgpVc3RlZCBkZWNsYXJhIHF1ZSBlbCBkb2N1bWVudG8gZXMgdW4gdHJhYmFqbyBvcmlnaW5hbCwgeSBxdWUgdGllbmUgZWwgZGVyZWNobyBkZSAKb3RvcmdhciBsb3MgZGVyZWNob3MgY29udGVuaWRvcyBlbiBlc3RhIGxpY2VuY2lhLiBUYW1iacOpbiBkZWNsYXJhIHF1ZSBzdSBwZXRpY2nDs24gCm5vIGluZnJpbmdlIGxvcyBkZXJlY2hvcyBkZSBhdXRvciBkZSBuYWRpZS4gCgpTaSBlbCBkb2N1bWVudG8gY29udGllbmUgbWF0ZXJpYWxlcyBwYXJhIGxvcyBxdWUgbm8gc2UgdGllbmVuIGxvcyBkZXJlY2hvcyBkZSBhdXRvciwgClVzdGVkIGRlY2xhcmEgcXVlIGhhIG9idGVuaWRvIGVsIHBlcm1pc28gc2luIHJlc3RyaWNjacOzbiBkZWwgcHJvcGlldGFyaW8gZGUgbG9zIApkZXJlY2hvcyB5IHF1ZSBlbiBkaWNobyBtYXRlcmlhbCwgZXN0w6EgY2xhcmFtZW50ZSBpZGVudGlmaWNhZGEgeSByZWNvbm9jaWRhIHN1IAphdXRvcsOtYSBkZW50cm8gZWwgdGV4dG8gbyBkZWwgY29udGVuaWRvIGRlIGRpY2hvIGRvY3VtZW50by4gCgpTaSBlbCBlbnbDrW8gc2UgYmFzYSBlbiB1biB0cmFiYWpvIHF1ZSBoYSBzaWRvIHBhdHJvY2luYWRvIG8gYXBveWFkbyBwb3IgdW5hIGFnZW5jaWEgCnUgb3JnYW5pemFjacOzbiBkaXN0aW50YSBhIFJFUElTQUxVRCwgdXN0ZWQgYWNlcHRhIHF1ZSBoYSBjdW1wbGlkbyBjb24gZWwgZGVyZWNobyBkZSAKcmV2aXNpw7NuIHkgb3RyYXMgb2JsaWdhY2lvbmVzIHJlcXVlcmlkYXMgcG9yIGNvbnRyYXRvIG8gYWN1ZXJkby4gCgpSRVBJU0FMVUQgaWRlbnRpZmljYXLDoSBjbGFyYW1lbnRlIHN1KHMpIG5vbWJyZShzKSBjb21vIGF1dG9yKHMpIG8gcHJvcGlldGFyaW8ocykgCmRlbCBkb2N1bWVudG8sIHkgbm8gaGFyw6EgbmluZ3VuYSBhbHRlcmFjacOzbiwgZXhjZXB0byBzZWfDum4gbG8gcGVybWl0aWRvIHBvciBlc3RhIApsaWNlbmNpYS4gCg==
URL
https://repisalud.isciii.es/bitstreams/797f02f7-2262-47a7-bc59-c08d459e9a0a/download
File
MD5
f3ae24a94d6d21ee9c165cf9e428e703
347034
application/pdf
PGC-1α Downregulation in Steatotic Liver_Antioxid Redox Signal_2017.pdf
URL
https://repisalud.isciii.es/bitstreams/ce3e9a2a-1369-4606-92b6-0ea78119065e/download
File
MD5
6f503778d17639021b2777ad76534092
53365
text/plain
PGC-1α Downregulation in Steatotic Liver_Antioxid Redox Signal_2017.pdf.txt