Protective effects of caspase-9 and poly(ADP-ribose) polymerase inhibitors on ischemia-reperfusion-induced myocardial injury

Sodhi, Rupinder Kaur; Singh, Manjeet; Singh, Nirmal; Jaggi, Amteshwar Singh

doi:10.1007/s12272-009-1709-9

Cited by 19 publications

(15 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is involved in a wide range of physiological processes including DNA repair, gene transcription and genomic stability maintenance, cell cycle progression, and apoptosis [18]. Several studies showed that inhibition of PARP has a protective effect on various organs during I/R [12][13][14]19]. In this study, increased concentration of MDA, an index of oxidative stress, and activation of PARP were strongly associated with increased apoptosis in the bladder after AUR and subsequent empting.…”

Section: Discussionsupporting

confidence: 51%

“…This is the main limitation of the present study. However, several recent reports have indicated that AUR not only induces bladder damage, but also induces functional and structural impairment of the heart, liver, and kidney [35][36][37] and inhibition of PARP-attenuated damage to several organs such as brain, kidney, liver, and heart under I/R conditions [12][13][14]19]. Considering these reports, we presume that inhibition of PARP may have beneficial effects on attenuating damage to other organs aside from the bladder.…”

Section: Discussionmentioning

confidence: 80%

“…Recent studies have demonstrated that an increase in PARP activity causes damage of several organs under I/R conditions such as ones seen in brain, kidney, and heart that is significantly attenuated by PARP inhibition [12][13][14]. Previously, a study in our laboratory showed that bladder apoptosis induced by AUR and subsequent bladder emptying is associated with increased PARP activity [15].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

PARP inhibition prevents oxidative injury of bladder induced by acute urinary retention and subsequent emptying

2011

Apoptosis

View full text Add to dashboard Cite

It has been demonstrated that increases in poly(ADP-ribose) polymerase (PARP) activity causes damage to several organs under ischemia/reperfusion (I/R) conditions. The aims of this study were to investigate whether inhibition of PARP could suppress apoptosis in the bladder following acute urinary retention (AUR) and subsequent bladder emptying. Twelve-week-old male Sprague Dawley rats were divided into a control group, saline treated group, and 3-aminobenzamide (3-AB, a specific PARP inhibitor)-treated group. Sixty minutes after the administration of saline and 3-AB, the saline and 3-AB-treated groups had 60 min of over-distension and followed by 2 h of drainage. The degree of bladder apoptosis, levels of malondialdehyde (MDA), ATP and nicotinamide adenine dinucleotide (NAD+); expression of poly(ADP-ribose) (PAR), phosphorylation of protein kinase B (Akt); and levels of Bcl-2, Bax, and caspase 3 activity in the bladder were determined. Molecular and histological analyses showed that bladder apoptosis was associated with increases in the amount of PAR and decreases in ATP and NAD+ levels in the saline treated group. In addition, phosphorylated Akt and Bcl-2/Bax ratio were significantly decreased. The activity of caspase 3 was significantly increased in the saline treated group. Inhibition of PARP significantly increased the levels of ATP and NAD+, phosphorylation of Akt, and Bcl-2/Bax ratio, and significantly reduced the activation of caspase 3. As a result, apoptosis in the bladder was attenuated. These results indicate that PARP activation may be involved in apoptosis in the bladder induced by AUR and subsequent emptying via energy depletion and suppression of Akt activity.

show abstract

Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

PARP inhibition prevents oxidative injury of bladder induced by acute urinary retention and subsequent emptying

2011

Apoptosis

View full text Add to dashboard Cite

show abstract

“…Studies have revealed that caspase-3 is the main apoptotic effect factor and the most important protease involved in cell apoptosis [32], while caspase-9 is required in most scenarios of apoptotic cell death. Numerous studies have demonstrated that caspase-9 [33] and caspase-3 [34] participate in myocardial infarction progression, and inhibition of caspase-9 [35] and caspase-3 [36] can significantly reduce ischemia-induced myocardial apoptosis with cardiac function improved. Our preliminary experiment showed that caspase-9 was activated after CME and that using caspase-9-specific inhibitor could significantly decrease myocardial apoptosis and improve cardiac function following CME [6].…”

Section: Discussionmentioning

confidence: 99%

Trimetazidine Pretreatment Inhibits Myocardial Apoptosis and Improves Cardiac Function in a Swine Model of Coronary Microembolization

Liu

et al. 2015

Cardiology

View full text Add to dashboard Cite

Objective: Trimetazidine (TMZ) is a well-known anti-ischemic agent; however, its efficacy and mechanism of cardioprotection on coronary microembolization (CME) are largely unknown. The present study was undertaken to determine whether TMZ pretreatment could attenuate myocardial apoptosis and improve cardiac function in a swine model of CME. Methods: Fifteen swine were randomly and equally divided into a sham-operated (control) group, CME group and CME plus TMZ (TMZ) group. CME was induced by injecting inert plastic microspheres (42 μm in diameter) into the left anterior descending artery. For the control group, the same dose of normal saline was substituted for the microspheres, and the TMZ group was pretreated with TMZ 30 min before microsphere injection. Cardiac function was assessed by echocardiography, myocardial apoptosis was detected by TUNEL staining, and the expression levels of cleaved caspase-9/3 were measured by Western blot 12 h after operation. Results: Compared to the control group, cardiac function in the CME group was significantly decreased (p < 0.05); however, TMZ pretreatment showed significantly improved cardiac function as compared to the CME group (p < 0.05). The myocardial apoptotic rate and the expression levels of cleaved caspase-9/3 increased remarkably in CME group as compared with the control group (p < 0.001). Again, TMZ pretreatment significantly reduced the apoptotic rate and also the expression levels of cleaved caspase-9/3 (p < 0.001). Conclusion: The present study demonstrated that TMZ pretreatment could significantly inhibit CME-induced myocardial apoptosis and improve cardiac function, and that the cardioprotective effect appeared to be mediated by the blockade of the mitochondrial apoptotic pathway. These results emphasize the importance of TMZ pretreatment in the therapy of CME-induced myocardial injury.

show abstract

“…In addition, we also examined the activity of poly (ADP-ribose) polymerase (PARP), because recent studies have demonstrated that increase in ROS following I/R injury increases PARP activity and causes damage in several organs, such as brain, kidney and the heart (12-14). …”

Section: Introductionmentioning

confidence: 99%

Time Dependent Bladder Apoptosis Induced by Acute Bladder Outlet Obstruction and Subsequent Emptying is Associated with Decreased MnSOD Expression and Bcl-2/Bax Ratio

Shin

2010

J Korean Med Sci

View full text Add to dashboard Cite

Ischemia/reperfusion (I/R) injury-induced oxidative stress plays an important role in the functional impairment of the bladder following acute bladder outlet obstruction (BOO) via induction of apoptosis. The purpose of this study was to investigate the time course of the bladder apoptosis, and apoptosis related molecular changes in the early stage of acute BOO. Twelve-week-old male Sprague Dawley rats were divided into control, acute BOO only (I), and acute BOO plus subsequent emptying (I/R) for 30, 60, 120 min, 3 days and 2 weeks. We examined the extent of bladder apoptosis, expression of Mn-superoxide dismutase (Mn-SOD), Bcl-2, Bax, caspase 3 and poly (ADP-ribose) (PAR) in the bladder. Bladder apoptosis was significantly increased in the I/R group at 30, 60, and 120 min following bladder emptying. BOO plus subsequent emptying for 30, 60, 120 min showed significant decrease in MnSOD and Bcl-2 expression, and significant increase in caspase 3, Bax expression, and amounts of PAR. These results indicate that bladder apoptosis, induced by acute BOO and subsequent emptying, is associated with decreased MnSOD expression, increased PARP activity and imbalance in apoptosis pathways.

show abstract

Protective effects of caspase-9 and poly(ADP-ribose) polymerase inhibitors on ischemia-reperfusion-induced myocardial injury

Cited by 19 publications

References 34 publications

PARP inhibition prevents oxidative injury of bladder induced by acute urinary retention and subsequent emptying

PARP inhibition prevents oxidative injury of bladder induced by acute urinary retention and subsequent emptying

Trimetazidine Pretreatment Inhibits Myocardial Apoptosis and Improves Cardiac Function in a Swine Model of Coronary Microembolization

Time Dependent Bladder Apoptosis Induced by Acute Bladder Outlet Obstruction and Subsequent Emptying is Associated with Decreased MnSOD Expression and Bcl-2/Bax Ratio

Contact Info

Product

Resources

About