Urocortin inhibits Beclin1-mediated autophagic cell death in cardiac myocytes exposed to ischaemia/reperfusion injury

Valentim, Lauren Martins; Laurence, Kevin M.; Townsend, Paul A.; Carroll, Christopher J.; Soond, Surinder M.; Scarabelli, Tiziano M.; Knight, Richard; Latchman, David S.; Stephanou, Anastasis

doi:10.1016/j.yjmcc.2006.03.428

Cited by 272 publications

(246 citation statements)

References 17 publications

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“…15 Neonatal and adult cardiac myocyte death induced by ischemia/reperfusion was also blocked in the presence of 3-methyladenine, or a knockdown of beclin1, in vitro. 62 These data suggest that activation of autophagy may be detrimental for the heart during ischemia/reperfusion. How the increased activity of autophagy, such as increased formation of autophagosomes and autophagic flux, leads to increased death of cardiac myocytes remains to be elucidated.…”

Section: Activation Of Autophagy By Hypoxia/ischemia and Reperfusionmentioning

confidence: 94%

“…60 As many BH3 domain-containing proteins are highly inducible, common mechanisms, such as HIF-1a for induction of Bnip3, may exist for induction of the BH3 domaincontaining protein family by ischemia/reperfusion. Upregulation of beclin1 after ischemia/reperfusion is suppressed by urocortin through activation of the PI3K/Akt pathway in cardiac myocytes, 62 which may protect the heart from excessive autophagy.…”

Section: The Mechanism Of Autophagy During Reperfusionmentioning

confidence: 99%

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The role of autophagy in the heart

Kyoi²,

et al. 2008

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Autophagy has evolved as a conserving process that uses bulk degradation and recycling of cytoplasmic components, such as long-lived proteins and organelles. In the heart, autophagy is important for the turnover of organelles at low basal levels under normal conditions and it is upregulated in response to stresses such as ischemia/reperfusion and in cardiovascular diseases such as heart failure. Cardiac remodeling involves increased rates of cardiomyocyte cell death and precedes heart failure. The simultaneously occurring multiple features of failing hearts include not only apoptosis and necrosis but also autophagy as well. However, it has been unclear as to whether autophagy is a sign of failed cardiomyocyte repair or is a suicide pathway for failing cardiomyocytes. The functional role of autophagy during ischemia/reperfusion in the heart is complex. It has also been unclear whether autophagy is protective or detrimental in response to ischemia/reperfusion in the heart. In this review, we will summarize the role of autophagy in the heart under both normal conditions and in response to stress.

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Section: Activation Of Autophagy By Hypoxia/ischemia and Reperfusionmentioning

confidence: 94%

Section: The Mechanism Of Autophagy During Reperfusionmentioning

confidence: 99%

The role of autophagy in the heart

Kyoi²,

et al. 2008

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“…A study using RNAi against Beclin 1 or 3-methyladenine (3-MA) treatment to block autophagy found that this resulted in reduced cell death in isolated cardiac mocytes subjected to sI/R, suggesting that autophagy contributes to cell death [12]. Moreover, glucose deprivation of H9c2 cells, a cell line derived from rat cardiac myocytes, caused an increase in autophagosomes and inhibiting autophagy with 3-MA or LY294002 reduced cell death [43].…”

Section: Autophagy In Ischemia and Reperfusionmentioning

confidence: 99%

“…It occurs at low basal levels under normal conditions and is important for the turnover of organelles [7]. Many studies have demonstrated that autophagy is upregulated in the heart in response to stress such as ischemia/reperfusion [4,[8][9][10][11][12]. Increased numbers of autophagosomes are a prominent feature in many cardiovascular diseases such as cardiac hypertrophy and heart failure [13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Recycle or die: The role of autophagy in cardioprotection

Gustafsson

Gottlieb

2008

Journal of Molecular and Cellular Cardiology

173

153

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Autophagy is a highly conserved cellular process responsible for the degradation of long-lived proteins and organelles. Autophagy occurs at low levels under normal conditions, but is upregulated in response to stress such as nutrient deprivation, hypoxia, mitochondrial dysfunction, and infection. Upregulation of autophagy may be beneficial to the cell by recycling of proteins to generate free amino acids and fatty acids needed to maintain energy production, by removing damaged organelles, and by preventing accumulation of protein aggragates. In contrast, there is evidence that enhanced autophagy can contribute to cell death, possibly through excessive self-digestion. In the heart, autophagy is essential role for maintaining cellular homeostasis under normal conditions and increased autophagy can be seen in conditions of starvation, ischemia/reperfusion, and heart failure. However, the functional significance of autophagy in heart disease is unclear and controversial. Here, we review the literature and discuss the evidence that autophagy can have both beneficial and detrimental roles in the myocardium depending on the level of autophagy, and discuss potential mechanisms by which autophagy provides protection in cells.

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“…Studies have reported that autophagy has a dual, opposite role in the heart, depending on the stimulus 7. Strategies that enhance autophagy can promote survival in response to milder stress, such as brief hypoxia and low levels of oxidative stress 6, 8, whereas severe stress, such as prolonged hypoxia or subsequent reperfusion, results in excessive autophagy, which may cause cell death by triggering excessive self‐digestion of essential proteins and organelles 9, 10. The manipulation of autophagy may represent a potential future therapeutic target to protect against ischaemia/reperfusion (I/R)‐induced cardiomyocyte death and preserve cardiac function.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‐21 protects against cardiac hypoxia/reoxygenation injury by inhibiting excessive autophagy in H9c2 cells via the Akt/mTOR pathway

Huang

Kong

et al. 2016

J Cellular Molecular Medi

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MicroRNAs and autophagy play critical roles in cardiac hypoxia/reoxygenation (H/R)‐induced injury. Here, we investigated the function of miR‐21 in regulating autophagy and identified the potential molecular mechanisms involved. To determine the role of miR‐21 in regulating autophagy, H9c2 cells were divided into the following six groups: control group, H/R group, (miR‐21+ H/R) group, (miR‐21‐negative control + H/R) group, (BEZ235+ H/R) group and (miR‐21+ BEZ235+ H/R) group. The cells underwent hypoxia for 1 hr and reoxygenation for 3 hrs. Cell count kit‐8 was used to evaluate cell function and apoptosis was analysed by Western blotting. Western blotting and transmission electron microscopy were used to investigate autophagy. We found that miR‐21 expression was down‐regulated, and autophagy was remarkably increased in H9c2 cells during H/R injury. Overexpression of miR‐21 with a miR‐21 precursor significantly inhibited autophagic activity and decreased apoptosis, accompanied by the activation of the AKT/mTOR pathway. In addition, treatment with BEZ235, a novel dual Akt/mTOR inhibitor, resulted in a significant increase in autophagy and apoptosis. However, we found that miR‐21‐mediated inhibition of apoptosis and autophagy was partly independent of Akt/mTOR activation, as demonstrated in cells treated with both miR‐21 and BEZ235. We showed that miR‐21 could inhibit H/R‐induced autophagy and apoptosis, which may be at least partially mediated by the Akt/mTOR signalling pathway.

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Urocortin inhibits Beclin1-mediated autophagic cell death in cardiac myocytes exposed to ischaemia/reperfusion injury

Cited by 272 publications

References 17 publications

The role of autophagy in the heart

The role of autophagy in the heart

Recycle or die: The role of autophagy in cardioprotection

MicroRNA‐21 protects against cardiac hypoxia/reoxygenation injury by inhibiting excessive autophagy in H9c2 cells via the Akt/mTOR pathway

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