The desumoylating enzyme sentrin-specific protease 3 contributes to myocardial ischemia reperfusion injury

Gao, Liang; Zhao, Yichao; He, Jie; Yang, Yan; Xu, Longwei; Lin, Nan; Ji, Qingqi; Tong, Renyang; Fu, Yanan; Gao, Yu; Su, Yuanyuan; Yuan, Ancai; He, Ben; Pu, Jun

doi:10.1016/j.jgg.2017.12.002

Cited by 21 publications

(25 citation statements)

References 39 publications

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“…While the overall changes of SENP3 levels were not clearly correlated to changes in overall total protein SUMO2/3-ylation, it is important to note that there are at least six separate members of the SENP family as well as other classes of SUMO proteases [9, 25]. Indeed, SENP1, SENP2 and SENP5 [26–28], as well as SENP3 [14], have each been strongly implicated in cardiac ischemia/reperfusion so it is likely that distinct subsets of SUMOylated proteins are regulated by different SENPs. Therefore, depending on the relative proportions, the impact of modulating levels of one SENP may not be apparent when assessing total global protein SUMOylation but, crucially, it is critical for the regulation of specific substrates.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, recent data also suggests a role for SENP3 in determining cardiomyocyte survival after ischemia-reperfusion, however whether SENP3 promotes cell survival or cell death remains controversial. It has been reported that SENP3 levels are upregulated in heart tissue in response to ischemia-reperfusion, and that knockdown of SENP3 in vivo reduces infarct size and improves cardiac function [14]. Similarly, in the cardiomyocyte H9C2 cell line, there is an increase in SENP3 levels in response to ischemia-reperfusion but, in contrast, knockdown of SENP3 promoted apoptosis after ischemia-reperfusion [15].…”

Section: Introductionmentioning

confidence: 99%

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Protective role of the deSUMOylating enzyme SENP3 in myocardial ischemia-reperfusion injury

et al. 2019

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Interruption of blood supply to the heart is a leading cause of death and disability. However, the molecular events that occur during heart ischemia, and how these changes prime consequent cell death upon reperfusion, are poorly understood. Protein SUMOylation is a post-translational modification that has been strongly implicated in the protection of cells against a variety of stressors, including ischemia-reperfusion. In particular, the SUMO2/3-specific protease SENP3 has emerged as an important determinant of cell survival after ischemic infarct. Here, we used the Langendorff perfusion model to examine changes in the levels and localisation of SUMOylated target proteins and SENP3 in whole heart. We observed a 50% loss of SENP3 from the cytosolic fraction of hearts after preconditioning, a 90% loss after ischemia and an 80% loss after ischemia-reperfusion. To examine these effects further, we performed ischemia and ischemia-reperfusion experiments in the cardiomyocyte H9C2 cell line. Similar to whole hearts, ischemia induced a decrease in cytosolic SENP3. Furthermore, shRNA-mediated knockdown of SENP3 led to an increase in the rate of cell death upon reperfusion. Together, our results indicate that cardiac ischemia dramatically alter levels of SENP3 and suggest that this may a mechanism to promote cell survival after ischemia-reperfusion in heart.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Protective role of the deSUMOylating enzyme SENP3 in myocardial ischemia-reperfusion injury

et al. 2019

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“…Very recently, two other papers have examined the role of SENP3 in cardiac cell survival after I/R (14,15). Both of those studies reported an increase in SENP3 levels following I/R in either whole heart or H9C2 cells.…”

Section: Discussionmentioning

confidence: 99%

“…We did not observe any changes in SENP3 levels in I/R samples and the reasons for this discrepancy are unclear. However, it remains possible that this is due (14).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, recent data also suggests a role for SENP3 in determining cardiomyocyte survival after ischaemia-reperfusion, however whether SENP3 promotes cell survival or cell death remains controversial. It has been reported that SENP3 levels are upregulated in heart tissue in response to ischaemiareperfusion, and that knockdown of SENP3 in vivo reduces infarct size and improves cardiac function (14). Similarly, in the cardiomyocyte H9C2 cell line, there is an increase in SENP3 levels in response to ischaemia-reperfusion but, in contrast, knockdown of SENP3 promoted apoptosis after ischaemia-reperfusion (15).…”

Section: Introductionmentioning

confidence: 98%

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Protective role of the deSUMOylating enzyme SENP3 in myocardial ischaemia-reperfusion injury

Rawlings

Lee

Seager

et al. 2019

Preprint

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Interruption of blood supply to the heart is a leading cause of death and disability. However, the molecular events that occur during heart ischaemia, and how these changes prime consequent cell death upon reperfusion, are poorly understood. Protein SUMOylation is a posttranslational modification that has been strongly implicated in the protection of cells against a variety of stressors, including ischaemia-reperfusion. In particular, the SUMO2/3-specific protease SENP3 has emerged as an important determinant of cell survival after ischaemic infarct. Here, we used the Langendorff perfusion model to examine changes in the levels and localisation of SUMOylated target proteins and SENP3 in whole heart. We observed a 50% loss of SENP3 from the cytosolic fraction of hearts after preconditioning, a 90% loss after ischaemia and an 80% loss after ischaemia-reperfusion. To examine these effects further, we performed ischaemia and ischaemia-reperfusion experiments in the cardiomyocyte H9C2 cell line. Similar to whole hearts, ischaemia induced a decrease in cytosolic SENP3. Furthermore, shRNA-mediated knockdown of SENP3 led to an increase in the rate of cell death upon reperfusion. Together, our results indicate that cardiac ischaemia dramatically alter levels of SENP3 and suggest that this may a mechanism to promote cell survival after ischaemiareperfusion in heart.

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SUMO‐specific proteases: SENPs in oxidative stress‐related signaling and diseases

Jiao,

Zhang,

Yang

2024

BioFactors

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Oxidative stress is employed to depict a series of responses detrimental to normal cellular functions resulting from an imbalance between intracellular oxidants, mainly reactive oxygen species and antioxidant defenses. Oxidative stress often contributes to the development of various diseases, including cancer, cardiovascular diseases, and neurodegenerative diseases. In this process, the relationship between small ubiquitin‐like modifier (SUMO) and oxidative stress has garnered significant attention, with its posttranslational modification (PTM) frequently serving as a marker of oxidative stress status. Sentrin/SUMO‐specific proteases (SENPs), affected by alternative splicing, PTMs such as phosphorylation and ubiquitination, and various protein interactions, are crucial molecules in the SUMO process. The human SENP family has six members (SENP1–3, SENP5–7), which are classified into two categories based on sequence similarity, substrate specificity, and subcellular location. They have two core functions in the human body: first, by cleaving the precursor SUMO and exposing the C‐terminal glycine, they initiate the SUMO process; second, they can specifically recognize and dissociate SUMO proteins bound to substrates, a process known as deSUMOylation. However, the connection between deSUMOylation and oxidative stress remains a relatively unexplored area despite their strong association with oxidative diseases such as cancer and cardiovascular disease. This article aims to illustrate the significant contribution of SENPs to the oxidative stress pathway through deSUMOylation by reviewing their structure and classification, their roles in oxidative stress, and the changes in their expression and activity in several typical oxidative stress‐related diseases.

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The desumoylating enzyme sentrin-specific protease 3 contributes to myocardial ischemia reperfusion injury

Cited by 21 publications

References 39 publications

Protective role of the deSUMOylating enzyme SENP3 in myocardial ischemia-reperfusion injury

Protective role of the deSUMOylating enzyme SENP3 in myocardial ischemia-reperfusion injury

Protective role of the deSUMOylating enzyme SENP3 in myocardial ischaemia-reperfusion injury

SUMO‐specific proteases: SENPs in oxidative stress‐related signaling and diseases

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