Dimerumic Acid and Deferricoprogen Activate Ak Mouse Strain Thymoma/Heme Oxygenase-1 Pathways and Prevent Apoptotic Cell Death in 6-Hydroxydopamine-Induced SH-SY5Y Cells

Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used antihyperglycemic agents for the treatment of type 2 diabetes mellitus. Recently, the pleiotropic actions of DPP-4 inhibitors have drawn much attention. In the present study, we aimed to examine whether gemigliptin, a recently developed DPP-4 inhibitor, could protect against cisplatin-induced nephrotoxicity. We showed that pretreatment with gemigliptin attenuated cisplatin-induced renal dysfunction, as shown by analysis of plasma creatinine levels and blood urea nitrogen and histological damage. Elevated plasma levels of active glucagon-like peptide-1 were observed in gemigliptin-pretreated mice after cisplatin treatment, compared to that in cisplatin alone-treated mice. Gemigliptin attenuated cisplatin-induced apoptotic cell death, as assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and Western blot analysis in the kidneys. Gemigliptin also decreased the plasma levels of tumor necrosis factor-αand monocyte chemoattractant protein-1 and attenuated nuclear staining of nuclear factor kappa-B p65 in the kidneys. In addition, gemigliptin increased the protein expression of heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1) in the kidneys of cisplatin-treated mice. Taken together, these results suggest that pretreatment with gemigliptin protects against cisplatin-induced nephrotoxicity in mice, possibly via inhibition of apoptotic cell death and inflammatory responses through induction of HO-1 and NQO1 expression.

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Higenamine reduces apoptotic cell death by induction of heme oxygenase-1 in rat myocardial ischemia-reperfusion injury

APOPTOSIS ◽

10.1007/s10495-006-7110-y ◽

2006 ◽

Vol 11 (7) ◽

pp. 1091-1100 ◽

Cited By ~ 63

Author(s):

Young Soo Lee ◽

Young Jin Kang ◽

Hye Jung Kim ◽

Min Kyu Park ◽

Han Geuk Seo ◽

...

Keyword(s):

Cell Death ◽

Myocardial Ischemia ◽

Reperfusion Injury ◽

Heme Oxygenase ◽

Ischemia Reperfusion Injury ◽

Apoptotic Cell ◽

Ischemia Reperfusion ◽

Heme Oxygenase 1 ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion

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The HIV protease inhibitor ritonavir synergizes with butyrate for induction of apoptotic cell death and mediates expression of heme oxygenase-1 in DLD-1 colon carcinoma cells

British Journal of Pharmacology ◽

10.1038/sj.bjp.0706023 ◽

2004 ◽

Vol 143 (7) ◽

pp. 890-898 ◽

Cited By ~ 12

Author(s):

Heiko Mühl ◽

Jens Paulukat ◽

Sonja Höfler ◽

Markus Hellmuth ◽

Rochus Franzen ◽

...

Keyword(s):

Cell Death ◽

Protease Inhibitor ◽

Colon Carcinoma ◽

Heme Oxygenase ◽

Apoptotic Cell ◽

Carcinoma Cells ◽

Hiv Protease ◽

Heme Oxygenase 1 ◽

Hiv Protease Inhibitor ◽

Colon Carcinoma Cells

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Heme oxygenase-1-mediated autophagy protects against pulmonary endothelial cell death and development of emphysema in cadmium-treated mice

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00097.2015 ◽

2015 ◽

Vol 309 (3) ◽

pp. L280-L292 ◽

Cited By ~ 41

Author(s):

Ranu Surolia ◽

Suman Karki ◽

Hyunki Kim ◽

Zhihong Yu ◽

Tejaswini Kulkarni ◽

...

Keyword(s):

Cell Death ◽

Lung Function ◽

Cigarette Smoke ◽

Heme Oxygenase ◽

Caspase 3 ◽

Apoptotic Cell ◽

Intratracheal Instillation ◽

Cigarette Smoke Exposure ◽

Heme Oxygenase 1 ◽

Micro Computed Tomography

Pulmonary exposure to cadmium, a major component of cigarette smoke, has a dramatic impact on lung function and the development of emphysema. Cigarette smoke exposure induces heme oxygenase-1 (HO-1), a cytoprotective enzyme. In this study, we employed a truncated mouse model of emphysema by intratracheal instillation of cadmium (CdCl2) solution (0.025% per 1 mg/kg body wt) in HO-1+/+, HO-1−/−, and overexpressing humanized HO-1 bacterial artificial chromosome (hHO-1BAC) mice. We evaluated the role of HO-1 in cadmium-induced emphysema in mice by analyzing histopathology, micro-computed tomography scans, and lung function tests. CdCl2-exposed HO-1−/− mice exhibited more severe emphysema compared with HO-1+/+ or hHO-1BAC mice. Loss of pulmonary endothelial cells (PECs) from the alveolar capillary membrane is recognized to be a target in emphysema. PECs from HO-1+/+, HO-1−/−, and hHO-1BAC were employed to define the underlying molecular mechanism for the protection from emphysema by HO-1. Electron microscopy, expression of autophagic markers (microtubule-associated protein 1B-light chain 3 II, autophagy protein 5, and Beclin1) and apoptotic marker (cleaved caspase 3) suggested induction of autophagy and apoptosis in PECs after CdCl2 treatment. CdCl2-treated HO-1−/− PECs exhibited downregulation of autophagic markers and significantly increased cleaved caspase 3 expression and activity (∼4-fold higher). Moreover, hHO-1BAC PECs demonstrated upregulated autophagy and absence of cleaved caspase 3 expression or activity. Pretreatment of HO-1+/+ PECs with rapamycin induced autophagy and resulted in reduced cell death upon cadmium treatment. Induction of autophagy following CdCl2 treatment was found to be protective from apoptotic cell death. HO-1 induced protective autophagy in PECs and mitigated cadmium-induced emphysema.

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Heme oxygenase and nitric oxide synthase mediate cooling‐associated protection against TNF‐α‐induced microcirculatory dysfunction and apoptotic cell death

The FASEB Journal ◽

10.1096/fj.02-0368com ◽

2003 ◽

Vol 17 (2) ◽

pp. 175-185 ◽

Cited By ~ 50

Author(s):

Michaela Amon ◽

Michael D. Menger ◽

Brigitte Vollmar

Keyword(s):

Nitric Oxide ◽

Cell Death ◽

Nitric Oxide Synthase ◽

Heme Oxygenase ◽

Apoptotic Cell ◽

Apoptotic Cell Death ◽

Microcirculatory Dysfunction ◽

Tnf Α ◽

Oxide Synthase

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Dual Targeting of the p38 MAPK-HO-1 Axis and cIAP1/XIAP by Demethoxycurcumin Triggers Caspase-Mediated Apoptotic Cell Death in Oral Squamous Cell Carcinoma Cells

Cancers ◽

10.3390/cancers12030703 ◽

2020 ◽

Vol 12 (3) ◽

pp. 703 ◽

Cited By ~ 4

Author(s):

Ming-Hsien Chien ◽

Wei-En Yang ◽

Yi-Chieh Yang ◽

Chia-Chi Ku ◽

Wei-Jiunn Lee ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Death ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

P38 Mapk ◽

Squamous Cell ◽

Apoptotic Cell ◽

Apoptotic Cell Death ◽

Heme Oxygenase 1 ◽

Caspase 8

Demethoxycurcumin (DMC) is a curcumin analogue with better stability and higher aqueous solubility than curcumin after oral ingestion and has the potential to treat diverse cancers, including oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the anticancer effects and underlying mechanisms of DMC against OSCC. We found that DMC suppressed cell proliferation via simultaneously inducing G2/M-phase arrest and cell apoptosis. Mechanistic investigations found that the downregulation of cellular IAP 1 (cIAP1)/X-chromosome-linked IAP (XIAP) and upregulation of heme oxygenase-1 (HO-1) were critical for DMC-induced caspase-8/-9/-3 activation and apoptotic cell death. Moreover, p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK)1/2 were activated by DMC treatment in OSCC cells, and only the inhibition of p38 MAPK significantly abolished DMC-induced HO-1 expression and caspase-8/-9/-3 activation. The analyses of clinical datasets revealed that patients with head and neck cancers expressing high HO-1 and low cIAP1 had the most favorable prognoses. Furthermore, a combinatorial treatment of DMC with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib, significantly enhanced the inhibitory effect of gefitinib on the proliferation of OSCC cells. Overall, the current study supported a role for DCM as part of a therapeutic approach for OSCC through suppressing IAPs and activating the p38-HO-1 axis.

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