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Chronic Treatment with a Water-Soluble Extract from the Culture Medium of Ganoderma lucidum Mycelia Prevents Apoptosis and Necroptosis in Hypoxia/Ischemia-Induced Injury of Type 2 Diabetic Mouse Brain.

Xuan M, Okazaki M, Iwata N, Asano S, Kamiuchi S, Matsuzaki H, Sakamoto T, Miyano Y, Iizuka H, Hibino Y - Evid Based Complement Alternat Med (2015)

Bottom Line: Pretreatment with MAK (1 g/kg, p.o.) for a week significantly reduced H/I-induced neurological deficits and brain infarction volume assessed at 24 h of reoxygenation.Histochemical analysis showed that MAK significantly suppressed superoxide production, neuronal cell death, and vacuolation in the ischemic penumbra, which was accompanied by a decrease in the numbers of TUNEL- or cleaved caspase-3-positive cells.Furthermore, MAK decreased the expression of receptor-interacting protein kinase 3 mRNA and protein, a key molecule for necroptosis.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunobiochemistry, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan ; Laboratory of Organic and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.

ABSTRACT
Type 2 diabetes mellitus has been known to increase systemic oxidative stress by chronic hyperglycemia and visceral obesity and aggravate cerebral ischemic injury. On the basis of our previous study regarding a water-soluble extract from the culture medium of Ganoderma lucidum mycelia (designed as MAK), which exerts antioxidative and neuroprotective effects, the present study was conducted to evaluate the preventive effects of MAK on apoptosis and necroptosis (a programmed necrosis) induced by hypoxia/ischemia (H/I) in type 2 diabetic KKAy mice. H/I was induced by a combination of unilateral common carotid artery ligation with hypoxia (8% O2 for 20 min) and subsequent reoxygenation. Pretreatment with MAK (1 g/kg, p.o.) for a week significantly reduced H/I-induced neurological deficits and brain infarction volume assessed at 24 h of reoxygenation. Histochemical analysis showed that MAK significantly suppressed superoxide production, neuronal cell death, and vacuolation in the ischemic penumbra, which was accompanied by a decrease in the numbers of TUNEL- or cleaved caspase-3-positive cells. Furthermore, MAK decreased the expression of receptor-interacting protein kinase 3 mRNA and protein, a key molecule for necroptosis. These results suggest that MAK confers resistance to apoptotic and necroptotic cell death and relieves H/I-induced cerebral ischemic injury in type 2 diabetic mice.

No MeSH data available.


Related in: MedlinePlus

Effects of chronic pretreatment with MAK (1 g/kg) on the expression of necroptotic factor gene expression after H/I. Expression levels of RIP1 (a) and RIP3 (b) mRNA at 6 (after 6 h) or 24 h (after 24 h) of reoxygenation after H/I in the penumbral cortex from the mice in each group, determined by real-time RT-PCR analysis.; n = 6–10 in each group. ∗∗, ∗∗∗P < 0.01, 0.001. ††P < 0.01 compared with the H/I-treated control group.
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fig6: Effects of chronic pretreatment with MAK (1 g/kg) on the expression of necroptotic factor gene expression after H/I. Expression levels of RIP1 (a) and RIP3 (b) mRNA at 6 (after 6 h) or 24 h (after 24 h) of reoxygenation after H/I in the penumbral cortex from the mice in each group, determined by real-time RT-PCR analysis.; n = 6–10 in each group. ∗∗, ∗∗∗P < 0.01, 0.001. ††P < 0.01 compared with the H/I-treated control group.

Mentions: The expression levels of RIP1 and RIP3 mRNA in the penumbral cortex for each group were quantified by real-time PCR. The expression of RIP1 mRNA showed no significant change by either H/I or MAK (1 g/kg)-treatment (Figure 6(a)). On the other hand, H/I increased the expression level of RIP3 mRNA, depending on the duration of reoxygenation (Figure 6(b)). RIP3 mRNA upregulation was prevented by pretreatment with MAK.


Chronic Treatment with a Water-Soluble Extract from the Culture Medium of Ganoderma lucidum Mycelia Prevents Apoptosis and Necroptosis in Hypoxia/Ischemia-Induced Injury of Type 2 Diabetic Mouse Brain.

Xuan M, Okazaki M, Iwata N, Asano S, Kamiuchi S, Matsuzaki H, Sakamoto T, Miyano Y, Iizuka H, Hibino Y - Evid Based Complement Alternat Med (2015)

Effects of chronic pretreatment with MAK (1 g/kg) on the expression of necroptotic factor gene expression after H/I. Expression levels of RIP1 (a) and RIP3 (b) mRNA at 6 (after 6 h) or 24 h (after 24 h) of reoxygenation after H/I in the penumbral cortex from the mice in each group, determined by real-time RT-PCR analysis.; n = 6–10 in each group. ∗∗, ∗∗∗P < 0.01, 0.001. ††P < 0.01 compared with the H/I-treated control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4402482&req=5

fig6: Effects of chronic pretreatment with MAK (1 g/kg) on the expression of necroptotic factor gene expression after H/I. Expression levels of RIP1 (a) and RIP3 (b) mRNA at 6 (after 6 h) or 24 h (after 24 h) of reoxygenation after H/I in the penumbral cortex from the mice in each group, determined by real-time RT-PCR analysis.; n = 6–10 in each group. ∗∗, ∗∗∗P < 0.01, 0.001. ††P < 0.01 compared with the H/I-treated control group.
Mentions: The expression levels of RIP1 and RIP3 mRNA in the penumbral cortex for each group were quantified by real-time PCR. The expression of RIP1 mRNA showed no significant change by either H/I or MAK (1 g/kg)-treatment (Figure 6(a)). On the other hand, H/I increased the expression level of RIP3 mRNA, depending on the duration of reoxygenation (Figure 6(b)). RIP3 mRNA upregulation was prevented by pretreatment with MAK.

Bottom Line: Pretreatment with MAK (1 g/kg, p.o.) for a week significantly reduced H/I-induced neurological deficits and brain infarction volume assessed at 24 h of reoxygenation.Histochemical analysis showed that MAK significantly suppressed superoxide production, neuronal cell death, and vacuolation in the ischemic penumbra, which was accompanied by a decrease in the numbers of TUNEL- or cleaved caspase-3-positive cells.Furthermore, MAK decreased the expression of receptor-interacting protein kinase 3 mRNA and protein, a key molecule for necroptosis.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunobiochemistry, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan ; Laboratory of Organic and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.

ABSTRACT
Type 2 diabetes mellitus has been known to increase systemic oxidative stress by chronic hyperglycemia and visceral obesity and aggravate cerebral ischemic injury. On the basis of our previous study regarding a water-soluble extract from the culture medium of Ganoderma lucidum mycelia (designed as MAK), which exerts antioxidative and neuroprotective effects, the present study was conducted to evaluate the preventive effects of MAK on apoptosis and necroptosis (a programmed necrosis) induced by hypoxia/ischemia (H/I) in type 2 diabetic KKAy mice. H/I was induced by a combination of unilateral common carotid artery ligation with hypoxia (8% O2 for 20 min) and subsequent reoxygenation. Pretreatment with MAK (1 g/kg, p.o.) for a week significantly reduced H/I-induced neurological deficits and brain infarction volume assessed at 24 h of reoxygenation. Histochemical analysis showed that MAK significantly suppressed superoxide production, neuronal cell death, and vacuolation in the ischemic penumbra, which was accompanied by a decrease in the numbers of TUNEL- or cleaved caspase-3-positive cells. Furthermore, MAK decreased the expression of receptor-interacting protein kinase 3 mRNA and protein, a key molecule for necroptosis. These results suggest that MAK confers resistance to apoptotic and necroptotic cell death and relieves H/I-induced cerebral ischemic injury in type 2 diabetic mice.

No MeSH data available.


Related in: MedlinePlus