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Tisp40 prevents cardiac ischemia/reperfusion injury through the hexosamine biosynthetic pathway in male mice

التفاصيل البيبلوغرافية
العنوان: Tisp40 prevents cardiac ischemia/reperfusion injury through the hexosamine biosynthetic pathway in male mice
المؤلفون: Xin Zhang, Can Hu, Zhen-Guo Ma, Min Hu, Xiao-Pin Yuan, Yu-Pei Yuan, Sha-Sha Wang, Chun-Yan Kong, Teng Teng, Qi-Zhu Tang
المصدر: Nature Communications, Vol 14, Iss 1, Pp 1-17 (2023)
بيانات النشر: Nature Portfolio, 2023.
سنة النشر: 2023
المجموعة: LCC:Science
مصطلحات موضوعية: Science
الوصف: Abstract The hexosamine biosynthetic pathway (HBP) produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to facilitate O-linked GlcNAc (O-GlcNAc) protein modifications, and subsequently enhance cell survival under lethal stresses. Transcript induced in spermiogenesis 40 (Tisp40) is an endoplasmic reticulum membrane-resident transcription factor and plays critical roles in cell homeostasis. Here, we show that Tisp40 expression, cleavage and nuclear accumulation are increased by cardiac ischemia/reperfusion (I/R) injury. Global Tisp40 deficiency exacerbates, whereas cardiomyocyte-restricted Tisp40 overexpression ameliorates I/R-induced oxidative stress, apoptosis and acute cardiac injury, and modulates cardiac remodeling and dysfunction following long-term observations in male mice. In addition, overexpression of nuclear Tisp40 is sufficient to attenuate cardiac I/R injury in vivo and in vitro. Mechanistic studies indicate that Tisp40 directly binds to a conserved unfolded protein response element (UPRE) of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter, and subsequently potentiates HBP flux and O-GlcNAc protein modifications. Moreover, we find that I/R-induced upregulation, cleavage and nuclear accumulation of Tisp40 in the heart are mediated by endoplasmic reticulum stress. Our findings identify Tisp40 as a cardiomyocyte-enriched UPR-associated transcription factor, and targeting Tisp40 may develop effective approaches to mitigate cardiac I/R injury.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2041-1723
Relation: https://doaj.org/toc/2041-1723
DOI: 10.1038/s41467-023-39159-0
URL الوصول: https://doaj.org/article/2783571945d74f9e96742f835e7dbbe6
رقم الأكسشن: edsdoj.2783571945d74f9e96742f835e7dbbe6
قاعدة البيانات: Directory of Open Access Journals
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