Treatment of Experimental Cerebral Vasospasm by Protein Transduction of Heme Oxygenase 1 (HO-1) Conjugated to a Residue of 11 Arginines

Ogawa, Tomoyuki; Hänggi, Daniel; Steiger, Hans‐Jakob

doi:10.1007/978-3-7091-0661-7_20

Cited by 2 publications

(2 citation statements)

References 16 publications

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“…In concert with nitric oxide (NO), 116 CO binds to and activates soluble guanylate cyclase (sGC), 117 a heme-containing protein that mediates smooth muscle relaxation, inhibits inflammation, and abrogates ischemic insult to neuronal cells. 118 Increases in the propensity for thrombosis 85 and in cerebral vasospasm 119 are changes observed in the HO-1-deficient mouse. In addition to modulating cerebral vascular resistance, the combination of sGC and GMP enhances neurotransmission and improves learning and memory, which are commonly impaired in patients with SLE and improved by UV-A1 irradiation.…”

Section: Ho-1 and The Central Nervous System (Cns)mentioning

confidence: 99%

Ultraviolet-A1 irradiation therapy for systemic lupus erythematosus

McGrath

2017

Lupus

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Systemic lupus erythematosus (lupus, SLE) is a chronic autoimmune disease characterized by the production of autoantibodies, which bind to antigens and are deposited within tissues to fix complement, resulting in widespread systemic inflammation. The studies presented herein are consistent with hyperpolarized, adenosine triphosphate (ATP)-deficient mitochondria being central to the disease process. These hyperpolarized mitochondria resist the depolarization required for activation-induced apoptosis. The mitochondrial ATP deficits add to this resistance to apoptosis and also reduce the macrophage energy that is needed to clear apoptotic bodies. In both cases, necrosis, the alternative pathway of cell death, results. Intracellular constituents spill into the blood and tissues, eliciting inflammatory responses directed at their removal. What results is “autoimmunity.” Ultraviolet (UV)-A1 photons have the capacity to remediate this aberrancy. Exogenous exposure to low-dose, full-body, UV-A1 radiation generates singlet oxygen. Singlet oxygen has two major palliative actions in patients with lupus and the UV-A1 photons themselves have several more. Singlet oxygen depolarizes the hyperpolarized mitochondrion, triggering non-ATP-dependent apoptosis that deters necrosis. Next, singlet oxygen activates the gene encoding heme oxygenase (HO-1), a major governor of systemic homeostasis. HO-1 catalyzes the degradation of the oxidant heme into biliverdin (converted to bilirubin), Fe, and carbon monoxide (CO), the first three of these exerting powerful antioxidant effects, and in conjunction with a fourth, CO, protecting against injury to the coronary arteries, the central nervous system, and the lungs. The UV-A1 photons themselves directly attenuate disease in lupus by reducing B cell activity, preventing the suppression of cell-mediated immunity, slowing an epigenetic progression toward SLE, and ameliorating discoid and subacute cutaneous lupus. Finally, a combination of these mechanisms reduces levels of anticardiolipin antibodies and protects during lupus pregnancy. Capping all of this is that UV-A1 irradiation is an essentially innocuous, highly manageable, and comfortable therapeutic agency.

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Section: Ho-1 and The Central Nervous System (Cns)mentioning

confidence: 99%

Ultraviolet-A1 irradiation therapy for systemic lupus erythematosus

McGrath

2017

Lupus

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“…HO-1, a 32-kDa microsomal enzyme [ 3 ], catalyzes the rate-limiting step in oxidative degradation of heme to CO, biliverdin (soon reduced to bilirubin) and iron [ 4 ]. Since its discovery [ 5 ], studies have shown that HO-1 plays an important role in many modern medical disciplines, such as critical care [ 6 – 8 ], pulmonology [ 9 – 11 ], nephrology [ 12 – 14 ], gastroenterology [ 15 – 17 ], cardiology [ 18 – 20 ], neurology [ 21 – 23 ] and transplant immunology [ 24 – 26 ]. Sofalcone increases HO-1 in human umbilical vein endothelial cells and blocks endothelial dysfunction [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Biliary tract external drainage increases the expression levels of heme oxygenase-1 in rat livers

et al. 2015

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BackgroundHeme oxygenase-1 (HO-1) protects cells by anti-oxidation, maintaining normal microcirculation and anti-inflammatory under stress. This study investigated the effects of biliary tract external drainage (BTED) on the expression levels of HO-1 in rat livers.MethodsBiliary tract external drainage was performed by inserting a cannula into the bile duct. Sixty Sprague–Dawley rats were randomized to the following groups: sham 1 h group; BTED 1 h group; bile duct ligation (BDL) 1 h group; sham 6 h group and BTED 6 h group. The expression levels of HO-1 mRNA were analyzed using real-time RT-PCR. The expression levels of HO-1 were analyzed using immunohistochemistry.ResultsThe expression levels of HO-1 mRNA in the liver of the BTED group increased significantly compared with the sham group 1 and 6 h after surgery (p < 0.05).The expression levels of HO-1 in the BTED group increased significantly compared with the sham group 1 and 6 h after surgery. The expression levels of HO-1 mRNA in the liver in the BDL group decreased significantly compared with the sham group 1 h after surgery (p < 0.05).The expression levels of HO-1 in the BDL group decreased significantly compared with the sham group at this time.ConclusionBiliary tract external drainages increase the expression levels of HO-1 in the liver.

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Treatment of Experimental Cerebral Vasospasm by Protein Transduction of Heme Oxygenase 1 (HO-1) Conjugated to a Residue of 11 Arginines

Abstract: These results suggest that the 11R-HO-1 protein transduction method has a potential to treat cerebral vasospasm.

Cited by 2 publications

References 16 publications

Ultraviolet-A1 irradiation therapy for systemic lupus erythematosus

Ultraviolet-A1 irradiation therapy for systemic lupus erythematosus

Biliary tract external drainage increases the expression levels of heme oxygenase-1 in rat livers

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