Impaired autophagy contributes to hepatocellular damage during ischemia/reperfusion: Heme oxygenase-1 as a possible regulator

Yun, Nari; Cho, Hong-Ik; Lee, Sun-Mee

doi:10.1016/j.freeradbiomed.2013.12.014

Cited by 48 publications

(34 citation statements)

References 44 publications

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“…The present study demonstrated that the inhibition of autophagy by hemin-activated HO-1 is significantly proportional to the effect of hemin on the scavenging of cellular free radicals. The current findings of HO-1-inhibited autophagy do not conflict with the results of previous studies performed in other types of cell, including hepatocytes and cardiomyocytes (30,31). In these previous studies, the induction of HO-1 enhanced, rather than attenuated, autophagy.…”

Section: Discussionsupporting

confidence: 57%

Heme oxygenase-1 protects H2O2-insulted glomerular mesangial cells from excessive autophagy

Wang

et al. 2016

Molecular Medicine Reports

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Abstract.Increasing evidence has demonstrated that the activation of heme oxygenase (HO)-1 reduces autophagy stimulated by oxidative stress injury, in which the supraphysiological production of reactive oxygen species (ROS) is detected. However, the potential mechanism underlying this effect remains unclear. The present study aimed to investigate the function of HO-1 activation in the regulation of autophagy in glomerular mesangial cells subjected to H 2 O 2 -induced oxidative stress injury. The results demonstrated that the HO-1 agonist, hemin, reduces the LC3 protein level, which was enhanced by H 2 O 2 treatment. Furthermore, hemin-activated HO-1 may function as a regulator of oxidative stress-induced autophagy in a dose-dependent manner. Pharmacological activation of c-Jun N-terminal kinase (JNK) inhibited the effect of hemin, indicating that the JNK signaling pathway is associated with the mechanism of HO-1 in impeding excessive autophagy. In addition to successfully alleviating H 2 O 2 -induced oxidative stress and cellular apoptosis, hemin-activated HO-1 may provide cytoprotection against rapamycin, a specific autophagy agonist. The present result suggested the inhibitory action of HO-1 in the avoidance of a potentially enhanced linkage between autophagy and apoptosis, particularly in the setting of excessive ROS. Therefore, enhancing the intracellular activity of HO-1 may assist the crosstalk between oxidative stress, autophagy and apoptosis, and represent a novel therapeutic strategy for renal ischemic disease. IntroductionPrevious investigation has demonstrated that heme oxygenase (HO), particularly the stress-responsive isoenzyme HO-1, exhibits vital regulatory functions in renal processes under pathophysiological conditions (1). Due to its beneficial effects, including oxidative stress relief and the inhibition of cell apoptosis, HO-1 has previously been proposed as a potential therapeutic target for ischemia/reperfusion or hypertension-induced glomerular injuries (2,3), and diabetic retinopathy (4). HO-1 has also been considered a potential biomarker of acute kidney injury (5). Multiple mechanisms may be involved in the protective effects of activated HO-1 (6). In a previous study, the effect of HO-1 in autophagy, an apoptosis-associated biological process, was also investigated, and an implication of the comprehensive understanding of the protective mechanisms of HO-1 was provided (7).Autophagy has been widely studied in the last decade (8). The mechanism of autophagy has been elucidated based on pathophysiology to understand human biology and disease (9-11). Autophagy must be reconsidered not only as a self-degrading strategy for cell survival, but also as a type of dynamic and systematic re-organization of cellular materials and energy (12). As such, an appropriate intervention strategy effecting autophagy may direct cellular materials and energy flow to intended processes in order to result in the alleviation of diseases. Therefore, targeting autophagy may be a non-limiting therapeutic strategy ...

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Section: Discussionsupporting

confidence: 57%

Heme oxygenase-1 protects H2O2-insulted glomerular mesangial cells from excessive autophagy

Wang

et al. 2016

Molecular Medicine Reports

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“…The 160 rats were randomly but evenly assigned to one of five groups: rats that received a sham operation (SH group) were submitted neither to the clamping procedure nor to drugs; rats in the IR group underwent IR treatment without drug delivery; rats in the CM group received 0.5% CMC-Na once a day for seven days, followed by IR; and rats in the OA group received 100 mg/kg OA once a day for seven days [16], followed by IR; on the basis of treatment in group OA, group OA+wortmannin further received 15 μ g/kg of PI3K inhibitor wortmannin, intraperitoneally, 30 min prior to hepatic IR [17]. OA suspension (20 mg/mL) was made with 0.5% CMC-Na aqueous solution.…”

Section: Methodsmentioning

confidence: 99%

Protective Effects of Pretreatment with Oleanolic Acid in Rats in the Acute Phase of Hepatic Ischemia-Reperfusion Injury: Role of the PI3K/Akt Pathway

Gui

Hua

Chen

et al. 2014

Mediators of Inflammation

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Oleanolic acid (OA) has been used to treat liver disorders, but whether it can attenuate hepatic ischemia-reperfusion- (IR-) associated liver dysfunction remains unexplored. In the present study, 160 male Sprague-Dawley rats were equally divided into five groups: group SH received neither hepatic IR nor drugs; group IR received hepatic IR without drugs; group CM and group OA received 0.5% sodium carboxymethylcellulose and 100 mg/kg OA, intragastrically, once a day for seven days before the hepatic IR, respectively; on the basis of treatment in group OA, group OA+wortmannin further received 15 μg/kg of PI3K inhibitor wortmannin, intraperitoneally, 30 min before the hepatic IR. Then each group was equally divided into four subgroups according to four time points (preoperation, 0 h, 3 h, and 6 h after reperfusion). Serum ALT activity, IL-1β concentration, and hepatic phosphorylation of PI3K, Akt, and GSK-3β protein expression were serially studied. We found that OA pretreatment improved histological status and decreased serum ALT and IL-1β levels. It also increased p-PI3K, p-Akt, and p-GSK-3β protein expression at all the four time points. Prophylactic wortmannin partially reversed OA's protective effects. The data indicate that OA pretreatment protects liver from IR injury during the acute phase partially through PI3K/Akt-mediated inactivation of GSK-3β.

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“…5A), have been observed in the socs1a-deficient liver (Table 3). These molecules have been reported to be involved in hypoxia-inducible responses and important regulators for mitochondrial biogenesis (43), physiological stress (3), LPL activity in peripheral tissues (9), and cytoprotection against oxidative stress during liver ischemia (41). Thus, our results above reveal that the depletion of socs1a causes a complex metabolic syndrome, including local hypoxia stress, progressive hepatic steatosis, and insulin resistance in fish.…”

Section: Discussionsupporting

confidence: 54%

Depletion of suppressor of cytokine signaling-1a causes hepatic steatosis and insulin resistance in zebrafish

Dai

Wang

Jin

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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Impaired autophagy contributes to hepatocellular damage during ischemia/reperfusion: Heme oxygenase-1 as a possible regulator

Cited by 48 publications

References 44 publications

Heme oxygenase-1 protects H2O2-insulted glomerular mesangial cells from excessive autophagy

Heme oxygenase-1 protects H2O2-insulted glomerular mesangial cells from excessive autophagy

Protective Effects of Pretreatment with Oleanolic Acid in Rats in the Acute Phase of Hepatic Ischemia-Reperfusion Injury: Role of the PI3K/Akt Pathway

Depletion of suppressor of cytokine signaling-1a causes hepatic steatosis and insulin resistance in zebrafish

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