The role of ALDH2 in tumorigenesis and tumor progression: Targeting ALDH2 as a potential cancer treatment

A major mitochondrial enzyme for protecting cells from acetaldehyde toxicity is aldehyde dehydrogenase 2 (ALDH2). The correlation between ALDH2 dysfunction and tumorigenesis/growth/metastasis has been widely reported. Either low or high ALDH2 expression contributes to tumor progression and varies among different tumor types. Furthermore, the ALDH2∗2 polymorphism (rs671) is the most common single nucleotide polymorphism (SNP) in Asia. Epidemiological studies associate ALDH2∗2 with tumorigenesis and progression. This study summarizes the essential functions and potential ALDH2 mechanisms in the occurrence, progression, and treatment of tumors in various types of cancer. Our study indicates that ALDH2 is a potential therapeutic target for cancer therapy.

Use of Purified Rabbit Serum Paraoxonase 1 Compared with the Traditional Method of Curative Effect on Dichlorvos-induced Liver Injury in Rats / 中国医科大学学报

Objective To explore whether the use of purified rabbit serum paraoxonase 1 (PON1) for the treatment of dichlorvos-induced liver injury in rats is superior to traditional method.Methods Thirty male SD rats were randomly divided into the followint 5 groups,with 6 rats in each group:control group (A group),dichlorvos group (B group),traditional treatment group (C group),PON 1 treatment group (D group),combined treatment group (E group).Rats in groups B,C,D and E were adminstered dichlorvos by intraperitoneal injection 9 mg/kg.In group C,atropine 10 mg/kg and iodine solution 45 mg/kg were injected intraperitoneally within 2 min after dichlorvos administration.In group D,PON1 was injected intravenously at a dose of 9 600 U/kg,30 min prior to poisoning.In group E,PON1 was injected intravenously at a dose of 9 600 U/kg,30 min prior to poisoning,followed by in travenous injection of atropine 10 mg/kg and iodine solution 45 rng/kg within 2 min after poisoning.Rats in A group received normal saline.Blood was collected at different time points to examine the acetyl cholinesterase (AChE)-levels by ELISA method.Liver tissue were collected at 12 hours after model establishment to observe the pathological changes.The expression of 4 hydroxy 2-nonenal (4-HNE) in the liver tissue was detected by immunohistochemistry and Western blotting.Results In group B,AChE levels decreased significantly,liver cells showed severn fatty degeneration,karyopyknosis and other pathological changes,and 4-HNE expression increased.The pathological changes of group D and group E were less obvious than those of group C,and the 4-HNE expression in the group D and group E were significantly different from that in the group C (P＜ 0.05).Conclusion PON1 plays a protective role in dichlorvos-induced liver injury in rats,and this protection is better than that offered by traditional treatment.

Low Retinal Dehydrogenase 1 (RALDH1) Level in Prepubertal Boys with Autism Spectrum Disorder: A Possible Link to Dopamine Dysfunction?

OBJECTIVE: Retinal dehydrogenase 1 (RALDH1) is a cytosolic enzyme which acts both as a source of retinoic acid (RA) and as a detoxification enzyme. RALDH1 has key functions in the midbrain dopaminergic system, which influences motivation, cognition, and social behavior. Since dopamine has been increasingly linked to autism spectrum disorder (ASD), we asked whether RALDH1 could contribute to the autistic phenotype. Therefore, we investigated for the first time the levels of RALDH1 in autistic patients. To further assess the detoxification function of RALDH1, we also explored 4-hydroxynonenal protein adducts (4-HNE PAs) and reduced glutathione (GSH) levels. Moreover, considering the effect of testosterone on RALDH1 expression, we measured the second to fourth digit ratio (2D:4D ratio) for both hands, which reflects exposure to prenatal testosterone. METHODS: Male patients with ASD (n=18; age, 62.9±4.3 months) and healthy controls (n=13; age, 78.1±4.9 months) were examined. Erythrocyte RALDH1, serum 4-HNE PAs and erythrocyte GSH levels were measured using colorimetric assays, and digit lengths were measured using digital calipers. RESULTS: We found significantly lower (−42.9%) RALDH1 levels in autistic patients as compared to controls (p=0.032). However, there was no difference in 4-HNE PAs levels (p=0.368), GSH levels (p=0.586), or 2D:4D ratios (p=0.246 in the left hand, p=0.584 in the right hand) between healthy controls and autistic subjects. CONCLUSION: We concluded that a subset of autistic patients had a low RALDH1 level. These results suggest that low RALDH1 levels could contribute to the autistic phenotype by reflecting a dopaminergic dysfunction.

Effect of cocaine-amphetamine-regulated transcript peptide on the content of 4-hydroxy-2-noneral and infarct volume after cerebral ischenia/reperfusion in mice / 国际脑血管病杂志

Objective To investigate the effect of cocaine-amphetamine-regulated transcript peptide (CART) on the content of 4-hydroxy-2-noneral (HNE) and infarct volume after cerebral ischemia/reperfusion in mice.Methods A total of 96 healthy male mice were randomly divided into four groups:ischemia/reperfusion (n =27),CART (n =27),normal saline control (n =27) and sham operation (n =15) groups.A middle cerebral artery occlusion (MCAO) model was induced.Two hours after MCAO,CART 55-102 and equivalent normal saline were injected respectively via the tail veins of mice in the CART group and the normal saline control group,and then they were injected every other 24 hour.The neurological scores,infarct volume and the HNE content of lipid metabolism of oxidative stress were performed and detected respectively at 12,24,48 and 72hours after reperfusion.Results CART could significantly improve the neurological deficit scores (all P ＜0.05) and reduce infarct volume (all P＜0.05) at different time points after ischemia/reperfusion.The content of HNE was upregulated (all P＜0.05) at different points after referfusion.CART could significantly down-regulate the increased HNE levd in brain after ischemia (all P＜0.05).Conclusions CART may protect ischemic brain injury in mice by inhibiting lipid peroxidation.