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Metabolic reprogramming is a common phenomenon in cancer, with aerobic glycolysis being one of its important characteristics. Hypoxia-inducible factor-1α (HIF1Α) is thought to play an important role in aerobic glycolysis. Meanwhile, naringin is a natural flavanone glycoside derived from grapefruits and many other citrus fruits. In this work, we identified glycolytic genes related to HIF1Α by analyzing the colon cancer database. The analysis of extracellular acidification rate and cell function verified the regulatory effects of HIF1Α overexpression on glycolysis, and the proliferation and migration of colon cancer cells. Moreover, naringin was used as an inhibitor of colon cancer cells to illustrate its effect on HIF1Α function. The results showed that the HIF1Α and enolase 2 (ENO2) levels in colon cancer tissues were highly correlated, and their high expression indicated a poor prognosis for colon cancer patients. Mechanistically, HIF1Α directly binds to the DNA promoter region and upregulates the transcription of ENO2; ectopic expression of ENO2 increased aerobic glycolysis in colon cancer cells. Most importantly, we found that the appropriate concentration of naringin inhibited the transcriptional activity of HIF1Α, which in turn decreased aerobic glycolysis in colon cancer cells. Generally, naringin reduces glycolysis in colon cancer cells by reducing the transcriptional activity of HIF1Α and the proliferation and invasion of colon cancer cells. This study helps to elucidate the relationship between colon cancer progression and glucose metabolism, and demonstrates the efficacy of naringin in the treatment of colon cancer.
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Humans , Glycolysis , Colonic Neoplasms/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Phosphopyruvate Hydratase/metabolism , Flavanones/pharmacology , Cell Line, Tumor , Databases, Genetic , Cell Proliferation/drug effects , Transfection , Warburg Effect, OncologicABSTRACT
Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.
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Objective To investigate the expression of ENO3 gene in hepatocellular carcinoma and its effect on the sensitivity of hepatocellular carcinoma cell lines to OXA, and to explore the possible mechanism. Methods qRT-PCR and immunohistochemical analysis were used to detect the expression of ENO3 in 48 pairs of hepatocellular carcinoma tissues and normal liver tissues.Overexpression plasmid was constructed and transfected into MHCC97H and HepG2 cells.The experiments were divided into empty group (Vector group), ENO3 overexpression group (ENO3 group), empty+OXA group (Vector+OXA group) and ENO3 overexpression+OXA group (ENO3+OXA group).The proliferation ability of MHCC97H and HepG2 cells were detected by CCK-8 assay and cell colony formation assay.The apoptosis rate was determined by flow cytometry assay.Protein expressions of Bcl-2, Bax and Caspase-3 were detected by Western blot assay. Results The expression of ENO3 was significantly decreased in hepatocellular carcinoma tissues, compared with normal liver tissues adjacent to the carcinoma.The expression of ENO3 gene in the ENO3 overexpression group was significantly higher than that in the empty group.Compared with the Vector+OXA group, cell viability was decreased, apoptosis rate was increased, Bcl-2 protein expression was decreased, Bax and Caspase-3 protein expression were increased in the ENO3+OXA group. Conclusion The expression of ENO3 is down-regulated in hepatocellular carcinoma tissues, and the overexpression of ENO3 can enhance the sensitivity of hepatocellular carcinoma cell lines to oxaliplatin by promoting cell apoptosis.
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@#[Abstract] Objective: To explore the effect of anti-ENO1 (enolase 1) antibody and metformin (MET) treatment on the proliferation, migration, invasion and stemness of cetuximab (CTX) -resistant non-small cell lung cancer (NSCLC) cells through targeting cancer stem cells and the possible mechanism. Methods: 10 mmol/L MET combined with 40 μg/ml anti-ENO1 antibody was used to treat CTX(35 µg/ml)-resistant NSCLC A549 cells for 4 d, and the effects of combined treatment on A549 cells were detected with proliferation experiment, colony formation assay, migration and invasion experiments and methylcellulose ball formation experiment. In the meanwhile, FCM was used to detect the effects of CTX, MET and anti-ENO1 antibody single-drug treatment as well as the three-drug combination treatment on ALDH+ and CD44+ lung cancer stem cell subsets. Results: CTX combined with MET and anti-ENO1 antibody treatment significantly inhibited the proliferation, migration, invasion and self-renewal capacity of A549 cells. FCM analysis found that MET could significantly inhibit ALDH+ stem cell subpopulations, while anti-ENO1 antibody could significantly inhibit CD44+ stem cell subpopulations, and the three-drug combination treatment could simultaneously suppress ALDH+ and CD44+ stem cell subpopulations. Conclusion: MET and anti-ENO1 antibody respectively target ALDH+ and CD44+ cancer stem cell subsets, and the combined treatment of MET and anti-ENO1 antibody can effectively reverse the resistance of A549 cells to CTX, and thereby more effectively inhibiting stemness, proliferation, metastasis of A549 cells and tumor recurrence.
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@# Objective: To investigate the effect of enolase 1 (ENO1) expression on proliferation, apoptosis and migration of lung cancer PC14 cells. Methods: ENO1 over-expression vector-pcDNA3.1/ENO1 was constructed and transfected into PC14 cells at logarithmic growth phase with liposome LipofectamineTM 2000. G418 was used to screen PC14 cells that stably expressing ENO1. The effects of ENO1 over-expression on proliferation, migration and apoptosis of PC14 cells were detected by CCK-8 method, scratch-healing assay and flow cytometry, respectively. Results: The ENO1 over-expression cell model was successfully constructed. Compared with PC14-vehicle and wild-type PC14 cells, the mRNA and protein expression levels of ENO1 in PC14-ENO1 cells were significantly elevated (all P<0.05), and the proliferation of PC14-ENO1 cells was significantly increased (all P<0.05). The relative mobility of PC14ENO1 cells was significantly higher than that of pcDNA3.1-vehicle cells and wild-type PC14 cells ([13.26±1.13]% vs [8.46±1.11]%, [7.86±1.00]%, both P<0.05). There was no significant difference in apoptotic rate among PC14-ENO1, PC14-vehicle and PC14 cells (all P> 0.05) Conclusion: Over-expression of ENO1 promotes proliferation and migration of lung cancer PC14 cells.
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Objective To investigate the expression and significance of FBXW7 and ENO1 in ovarian serous adenocarcinoma of different grades. Methods Immunohistochemistry was used to study the expression of FBXW7 and ENO1 in 60 cases of ovarian serous adenocarcinoma. The relationship between FBXW7 and ENO1 proteins and the prognosis of ovarian serous adenocarcinoma was analyzed. Results The positive rate of FBXW7 expression was 22. 5% ( 9/40) in 40 cases of ovarian high grade adenocarcinoma and 10 cases in 15 cases of normal oviduct. The positive rate of FBXW7 expression was 66. 7% ( 10/15) ,and the difference was statistically significant ( P=0. 003) . The expression of FBXW7 in 20 cases of low grade adenocarcinoma was 5 cases,and the positive rate was 25. 0%( 5/20) . In 15 cases of normal ovarian tissue,9 cases were positive,and the positive rate was 60. 0%( 9/15) . The difference was statistically significant ( P=0. 04) . The expression of ENO1 protein was 27 in 40 cases of high grade adenocarcinoma,and the positive rate of expression was 67. 5%( 27/40) . 5 cases were positive in 15 normal fallopian tubes, and the positive rate was 33. 3%( 5/15 ) . The difference was statistically significant ( P = 0. 024 ) . The expression of ENO1 protein was 15 in 20 cases of low grade adenocarcinoma,and the positive rate of expression was 75. 0%( 15/20) . In 15 cases of normal ovarian tissue,4 cases were positive, and the positive rate was 26. 7%( 4/15 ) . The difference was statistically significant ( P=0. 006) . There was no correlation between the low expression of FBXW7 and the high expression of ENO1 in high grade ovarian adenocarcinoma ( P= 0. 199 ) , but there was a significant correlation between the low expression of FBXW7 and the high expression of ENO1 in low grade ovarian adenocarcinoma ( P<0. 05) . In low grade serous adenocarcinoma,the 5-year survival rates were 44. 4% and 32. 1% respectively,with no significant difference ( P = 0. 052 ) . In ovarian high-grade serous adenocarcinoma, the 5-year survival rates of high-expression group and low-expression group were 20. 0% and 7. 7%, respectively, with no significant difference ( P=0. 097) . In low grade ovarian serous adenocarcinoma,the 5-year survival rate was 7. 4% in high expression group and 50. 0% in low expression group ( P=0. 023) . The 5-year survival rates of ENO1 in high-grade serous adenocarcinoma were 0% and 40. 0% in high-expression group and low-expression group respectively ( P=0. 001) . Conclusion The low expression of FBXW7 in ovarian adenocarcinoma suggests that FBXW7 may be a tumor suppressor gene in ovarian serous adenocarcinoma, and ENO1 may be an oncogene in ovarian adenocarcinoma. The high expression of FBXW7 in serous adenocarcinoma indicates that ENO1 may be an oncogene,and the survival rate of FBXW7 in serous adenocarcinoma is higher than that in low expression group. The survival rate of the high-expression group was lower than that of the low-expression group. Therefore, they may become a new diagnostic index and therapeutic target for ovarian serous adenocarcinoma.
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Objective:To investigate the relationship between ciaH, eno, pykF genes and fluoride resistance through determining the differential expressions of ciaH, eno and pykF genes of fluoride-resistant Streptococcus mutans cultivated in fluoride environment. Methods:The cultured Streptococcus mutans and their fluoride-resistant strains were divided into UA (Streptococcus mutans subcultured in BHI without NaF), FR (fluoride-resistant Streptococcus mutans subcultured in BHI without NaF) and FFR (fluoride-resistant Streptococcus mutans subcultured in BHI containing 1 g·L-1 NaF) groups.After 11 h (logarithmic phase) and 20 h (platform stage) cultivation, the expression levels of ciaH, eno and pykF mRNA were detected by RT-PCR method.Results:Compared with FR group, the expression levels of ciaH, eno and pykF mRNA in FFR group were increased both in the logarithmic phase and the platform stage(P0.05), but it was increased in the platform stage (P<0.01).Conclusion:Fluoride can increase the expression levels of ciaH, eno and pykF genes in fluoride-resistant Streptococcus mutans, indicating that these genes are related to the production of fluoride resistance.
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Objective@#To investigate the role of enolase 1 (ENO1) in hepatocellular carcinoma (HCC) and possible mechanism.@*Methods@#Real-time PCR and Western blot were used to measure the expression of ENO1 in HCC tissue, adjacent tissue, hepatoma cells, and normal hepatocytes. The siRNA interference technique was used for ENO1 knockout in HepG2 cells, and then CCK-8, colony formation assay, and transwell assay were used to measure the proliferation, migration, and invasion abilities of HepG2 cells. Real-time PCR and Western blot were used to measure the expression of proteins and genes involved in the activation of the Notch signaling pathway. The two-independent-samples t test and a one-way analysis of variance were used for comparison.@*Results@#HCC tissue and HepG2 cells had significantly higher expression of ENO1 than adjacent tissue and normal hepatocytes (P < 0.05). There were significant reductions in the proliferation, migration, and invasion abilities of HepG2 cells after siRNA interference (P < 0.05). There were also significant reductions in the expression of N1ICD, snail, slug, HEY1, HES1, and HES5 (P < 0.05).@*Conclusion@#ENO1 may promote the development of HCC, possibly by participating in the regulation of the Notch signaling pathway.
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Objective To observe the serum concentration of S100βprotein (S100β)and neuron specific enolase (NSE)in patients undergoing supratentorial tumor resection with ulinastatin treat-ment.Methods Twenty-four patients with supratentorial tumor resection,aged 18-65 years,ASA Ⅰor Ⅱ,were randomly divided into the control group (group A,n =12)and ulinastatin group (group U,n =12).Patients in group U received ulinastatin (2 kU/kg)at the beginning of the surgery,with the continuous dose of 1 kU·kg-1 ·h-1 till the end of the operation.Group A received equivalent volume of saline solution as the vehicle control.Blood samples were taken from the artery and jugular venous bulb before induction of anesthesia (T1 ),skin incision (T2 ),1 h after dura openning (T3 ),at the closure of dura (T4 ),at the end of operation (T5 )and 24 h after operation (T6 )to analyze the concentration of S100β and NSE.The concentration of S100β and NSE were determined by ELISA. Results The concentration of serum S100β and NSE increased more significantly higher at T3-T6 in group A than group U (P <0.01).The concentration of serum S100βand NSE in group U were lower than those in group A at T3-T5 (P < 0.01 ).Conclusion Ulinastatin reduces the concentration of serum S100βand NSE during surgery,indicating it alleviates brain injury during supratentorial tumor resection.
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GV1001 is a peptide derived from the human telomerase reverse transcriptase (hTERT) sequence that is reported to have anti-cancer and anti-inflammatory effects. Enolase1 (ENO1) is a glycolytic enzyme, and stimulation of this enzyme induces high levels of pro-inflammatory cytokines from concanavalin A (Con A)-activated peripheral blood mononuclear cells (PBMCs) and ENO1-expressing monocytes in healthy subjects, as well as from macrophages in rheumatoid arthritis (RA) patients. Therefore, this study investigated whether GV1001 downregulates ENO1-induced pro-inflammatory cytokines as an anti-inflammatory peptide. The results showed that GV1001 does not affect the expression of ENO1 in either Con A-activated PBMCs or RA PBMCs. However, ENO1 stimulation increased the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6, and these cytokines were downregulated by pretreatment with GV1001. Moreover, p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappaB were activated when ENO1, on the surface of Con A-activated PBMCs and RA PBMCs, was stimulated, and they were successfully suppressed by pre-treatment with GV1001. These results suggest that GV1001 may be an effective anti-inflammatory peptide that downregulates the production of pro-inflammatory cytokines through the suppression of p38 MAPK and NF-kappaB activation following ENO1 stimulation.
Subject(s)
Humans , Arthritis, Rheumatoid , Concanavalin A , Cytokines , Down-Regulation , Inflammation , Interleukin-6 , Interleukins , Macrophages , Monocytes , NF-kappa B , p38 Mitogen-Activated Protein Kinases , Protein Kinases , Telomerase , Tumor Necrosis Factor-alphaABSTRACT
Aim Drug resistance is one of the major hinders on cancer treatments. α-enolase ( eno1 ) was closely related to the generation and development of drug resistance. This article aims to study the effect of eno1 on cell growth and drug resistance in human chro-nic myeloid leukemia cell line K562/A02 . Methods We screened three eno1 stable silencing cells K562/A02-sheno1 and its control cells K562/A02-shcon. Cell count assay was performed to test cell growth, MTT assay was used to test cell proliferation, flow cytometry was used to test the intra-cellular Rho123 content, the expression of genes were tested by real-time PCR assay and western blot assay on mRNA level and protein level, respectively. Results eno1 was o-ver-expressed in K562/A02 cells and its expression was increased by ( 2. 85 ± 0. 56 ) times and ( 1. 43 ± 0. 05 ) times on mRNA level and protein level com-pared to K562 cells. However, there was no difference in cell growth rate between K562/A02 cells and K562 cells. K562/A02-sheno1 cells showed lower cell growth rate and higher drug sensitivity to anti-cancer drugs taxol and doxorubicin. Moreover the Rho123 content was increased in K562/A02-sheno1 cells. The expression of MDR1 decreased in both mRNA level and protein level in K562/A02-sheno1 cells. Conclusion eno1 silencing could suppress cell growth, reverse drug resistance and increase its drug sensitivity in K562/A02 cells, and the mechanism was associated with the MDR1 gene.
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El grupo de las encefalitis Equina Venezolana, del Este, del Oeste y del Nilo Occidental (EEV, EEE, EEO y ENO respectivamente) son zoonosis transmitidas por mosquitos a humanos y equinos. Este grupo de enfermedades se mantienen en la naturaleza en ciclos enzoóticos de transmisión entre mosquitos y roedores silvestres o aves que son sus hospedadores naturales. La circulación de estos virus es enzoótica y ocurre en áreas geográficas definidas y tienen capacidad de causar epidemias/epizootias con morbilidad y mortalidad que puede ser de importancia significativa. Este artículo describe detalladamente todas las encefalitis virales que afectan a los équidos y sus aspectos clínicos, patológicos y diagnósticos.
The encephalitis of Venezuelan Equine, Eastern, Western and West Nile (VEE, EEE, WEE and ENO respectively) are zoonotic encephalitis transmitted by mosquitoes to humans and horses. This group of diseases is maintained in nature in cycles enzootic transmission between mosquitoes and wild rodents or birds are their natural hosts. The circulation of this virus is enzootic and occurs in defined geographical areas but is capable of causing epidemics / epizootics with morbidity and mortality can be significant importance. This article describes all viral encephalitis affecting equines and their clinical, pathological and diagnostic aspects.
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Humans , Animals , Male , Female , Child, Preschool , Child , Adolescent , Adult , Middle Aged , Viruses/classification , Encephalitis/complications , Encephalitis/pathology , Epidemics/prevention & control , Encephalomyelitis, Equine/transmission , CulicidaeABSTRACT
Resumen: Arch Med Interna 2013 - 35(1):05-08 Las complicaciones neurológicas son frecuentes en los pacientes afectados por el virus de inmunodeficiencia humana (VIH). Se realizó un estudio descriptivo, retrospectivo, para conocer la frecuencia de la patología neurológica en los pacientes VIH/SIDA (síndrome de inmunodeficiencia adquirida) de nuestro centro, su perfil clínico y evolutivo, comparar el grado de inmunodepresión, el tiempo de estadía hospitalaria, la gravedad de la afección (estimada por requerimiento de ingreso a CTI) y la mortalidad entre los pacientes que se presentaban con enfermedades oportunistas (EO) y enfermedades no oportunistas (ENO). Se encontró una alta prevalencia de enfermedad neurológica (21%), en población joven, en su mayoría de sexo masculino, con inmunodepresión muy severa, predominando la etapa SIDA; las EO son las más frecuentes y registran mayor morbimortalidad que las ENO. Nuestra población no registra la transición epidemiológica del mundo desarrollado vinculado al uso de terapia antirretroviral (TARV), hecho que atribuímos a sus condiciones socio-económico-culturales.
Abstract: Arch Med Interna 2013 - 35(1):05-08 Neurological complications are common in patients with human immunodeficiency virus (HIV). We conducted a descriptive study, to determine the frequency of neurological disease in HIV/AIDS (acquired immunodeficiency syndrome) in our center, their clinical and developmental profile, and compare the degree of immunosuppression, the length of hospital stay, severity of the condition (estimated income requirement to intensive care unit [ICU]) and mortality between the patients presenting with opportunistic disease (OD) and non-opportunistic disease (NOD). High prevalence of neurological disease (21%) was found, mostly in young people, male, with severe immunosuppression, dominating the AIDS stage. ODs are more frequent and have higher recorded morbidity than NOD. Our population does not record the epidemiological transition seen in the developed world linked to the use of antiretroviral therapy (ART), a fact we attribute to the socio-economic-cultural situation.
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BACKGROUND: CM1 (centrocyte/-blast marker 1) was defined by a mAb against concanavalin A (Con A) activated PBMC. It is expressed in germinal center of human tonsil and on the surface of activated PBMC as well as cancer cells. Recently, increased productions of pro-inflammatory mediators were detected from activated PBMC by CM1 ligation. METHODS: However, there is a limitation to explain the exact role of CM1 on inflammation and its related mechanisms, since the identity of CM1 is still not clarified. In our previous study, we have already confirmed that soluble form of CM1 was produced by Raji. Therefore, we performed Q-TOF analysis after immunoprecipitation of concentrated Raji culture supernatant using anti-CM1 mAbs. RESULTS: As a result, we found that CM1 is identical to enolase-1(ENO1), a glycolytic enzyme, and we confirmed that results by silencing ENO1 using siRNA. It was also confirmed through competition assay between anti-CM1 and anti-ENO1 mAbs. Finally, we investigated the possible role of CM1 in inflammatory response and cancer. The ligation of CM1 on Raji cells with anti-CM1 mAbs induces the extensive production of prostaglandin E2(PGE2). In addition, the increased activity of matrix metalloproteinase (MMP)-2/9 was shown in NCI-N87, stomach cancer cell line by CM1 stimulation. CONCLUSION: CM1 is identical to ENO1 and it might be an important role in the regulation of inflammatory responses.
Subject(s)
Humans , Cell Line , Concanavalin A , Dinoprostone , Germinal Center , Immunoprecipitation , Inflammation , Ligation , Palatine Tonsil , RNA, Small Interfering , Stomach NeoplasmsABSTRACT
The large catfishes, genus Hypostomus Lacépède, are common species in almost all freshwater environments of South America. The behavior of specimens from the species Hypostomus alatus, Hypostomus francisci, Hypostomus cf. wuchereri, and Hypostomus sp., from the region downstream from the Xingó Hydroelectric Power Dam, located in Canindé do São Francisco on the Rio São Francisco, were observed. Morphological characters collected from preserved specimens were also studied in the laboratory, in order to shed light on interactions between those fishes and the river bottom. In addition, the formulation of Gatz (1979) was applied to better explain the environmental interactions of Hypostomus species. This study revealed that the fishes utilize their suckers, through a mouth equipped with an oral disk, as well as the pectoral, pelvic, and caudal fins areas, to interact with the rocky river-bottom. The comb-toothed inferior mouth of the Hypostomus showed itself able to grasp green algae on the river bottom. With the help of the oral disk and sucker mouth, which anchor the fishes, in conjunction with the arched design of pectoral and pelvic fin spines, they are also able to remain upright while exploring this substratum. In addition, their large, concave caudal-fin is associated with fast locomotion over short distances. This combination of characteristics allow these fish to live on the bottom of large South American rivers.
Os "cascudos" do gênero Hypostomus são comuns em todos os ambientes de água doce da América do Sul. O comportamento de peixes pertencentes a quatro espécies desse gênero, Hypostomus alatus, Hypostomus francisci, Hypostomus cf. wuchereri e Hypostomus sp., foi observado. A morfologia externa também foi estudada em espécimes preservados em coleção procedentes da localidade de Canindé do São Francisco, em regiões a jusante da usina hidroelétrica de Xingó, Estado de Sergipe. Foram estudados caracteres anatômicos e o protocolo de equações descritas por Gatz (1979) foi utilizado para explicar algumas das interações dos peixes com o ambiente bentônico do rio. Os resultados revelaram que os peixes se utilizam da região bucal através do disco oral que produz forte ação suctória e das nadadeiras pares para se equilibrarem no fundo rochoso do rio São Francisco. Descreve-se ainda a ação dos espinhos das nadadeiras peitorais e pélvicas em arco, que permitem aos peixes se ancorarem horizontalmente sobre o fundo do rio. A nadadeira caudal tem formato entalhado, promovendo locomoção rápida na coluna de água. É ainda discutida a ação dos dentes móveis e em forma de pente, que atuam na raspagem de algas que crescem sobre as rochas do fundo. A atuação desses caracteres de maneira associada sugere que as espécies do gênero Hypostomus devem habitar e interagir com o ambiente bentônico dos rios maiores da América do Sul.