Alcohol metabolism by oral streptococci and interaction with human papillomavirus leads to malignant transformation of oral keratinocytes.
Alcohol metabolism by oral streptococci and interaction with human papillomavirus leads to malignant transformation of oral keratinocytes.
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DOI：
10.1007/978-3-319-09614-8_14
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发表时间：
2015
影响因子：
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通讯作者：
L. Tao;S. Pavlova;Stephen R Gasparovich;Ling Jin;Joel Schwartz
中科院分区：
文献类型：
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作者：
L. Tao;S. Pavlova;Stephen R Gasparovich;Ling Jin;Joel Schwartz
口腔卫生不良、酒精消耗和人乳头瘤病毒（HPV）与口腔癌和食管癌有关。然而，其机制尚不完全清楚。本研究探讨了链球菌的酒精代谢及其与HPV-16在口腔角质形成细胞恶性转化中的相互作用。分析了产乙酰丙酮酸的戈登链球菌V2016的粘附基因和醇醛脱氢酶活性，研究了链球菌对永生化HPV-16感染的人口腔角质形成细胞、HOK（HPV/HOK-16 B）、人口腔颊粘膜角质形成细胞和包皮角质形成细胞的粘附。乙醛，丙二醛，DNA损伤，角质形成细胞中的异常增殖也进行了量化。我们发现S。gordoniIV 2016表达三种伯醇脱氢酶AdhA、AdhB和AdhE，它们都将乙醇氧化成乙醛，但它们的优选底物分别是1-丙醇、1-丁醇和乙醇。gordoniIV 2016没有显示可检测的醛脱氢酶。AdhE是戈登链霉菌中主要的醇脱氢酶。乙醛和丙二醛生产从允许的链球菌种显着增加细菌附着角质形成细胞，这是与弗林蛋白酶的表达增强，以促进HPV感染和几种恶性表型，包括乙醛加合物的形成，异常增殖，并增强迁移通过整合素包被的基底膜HPV感染的口腔角质形成细胞。因此，没有功能性醛脱氢酶的多种醇脱氢酶的表达有助于口腔链球菌从乙醇过度产生乙醛。口腔链球菌和HPV可能在乙醇暴露后协同转化口腔角质形成细胞。这些结果表明，一个显着的临床相互作用，但需要进一步验证。
Poor oral hygiene, ethanol consumption, and human papillomavirus (HPV) are associated with oral and esophageal cancers. However, the mechanism is not fully known. This study examines alcohol metabolism inStreptococcusand its interaction with HPV-16 in the malignant transformation of oral keratinocytes. The acetaldehyde-producing strainStreptococcus gordoniiV2016 was analyzed foradhgenes and activities of alcohol and aldehyde dehydrogenases.Streptococcusattachment to immortalized HPV-16 infected human oral keratinocytes, HOK (HPV/HOK-16B), human oral buccal keratinocytes, and foreskin keratinocytes was studied. Acetaldehyde, malondialdehyde, DNA damage, and abnormal proliferation among keratinocytes were also quantified. We found thatS. gordoniiV2016 expressed three primary alcohol dehydrogenases, AdhA, AdhB, and AdhE, which all oxidize ethanol to acetaldehyde, but their preferred substrates were 1-propanol, 1-butanol, and ethanol, respectively.S. gordoniiV2016 did not show a detectable aldehyde dehydrogenase. AdhE is the major alcohol dehydrogenase inS. gordonii. Acetaldehyde and malondialdehyde production from permissibleStreptococcusspecies significantly increased the bacterial attachment to keratinocytes, which was associated with an enhanced expression of furin to facilitate HPV infection and several malignant phenotypes including acetaldehyde adduct formation, abnormal proliferation, and enhanced migration through integrin-coated basement membrane by HPV-infected oral keratinocytes. Therefore, expression of multiple alcohol dehydrogenases with no functional aldehyde dehydrogenase contributes to excessive production of acetaldehyde from ethanol by oral streptococci. OralStreptococcusspecies and HPV may cooperate to transform oral keratinocytes after ethanol exposure. These results suggest a significant clinical interaction, but further validation is warranted.