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These Dihia Allane V Bibilio N° d’ordre : 61/2018-C/S.B REPUBLIQUE ALGERIENNE DEMOCRATIQUE ET POPULAIRE Ministère De L’ enseignement Supérieur et de la Recherche Scientifique Université des Sciences et de la Technologie Houari Boumediène Faculté des Sciences Biologiques THÈSE Présentée pour l’obtention du diplôme de Doctorat 3 ème Cycle (LMD) En : SCIENCES BIOLOGIQUES Spécialité : Biochimie-Immunologie et Biothérapies Innovantes Présentée par Dihia ALLANE THÈME Étude et caractérisation de l’activité anti -leishmanienne du venin de Cerastes cerastes Soutenue publiquement, le 12 / 07 / 2018, devant le jury: Mm F. LARABA-DJEBARI Professeur à l’ USTHB Présidente Mm H. OUSSEDIK-OUMEHDI Professeur à l’ USTHB Directeur de thèse Mr A. MATI Professeur à l’ UMMTO Examinateur Mr Z. HARRAT Professeur à L’IPA Examinateur Mm H. BOUKHALFA-ABIB Maitre de Conférences A à l’ USTHB Examinateur Mr F. CHERIFI Maitre de Conférences A à l’ USTHB Examinateur Au nom d'Allah, le Tout Miséricordieux, le Très Miséricordieux Remerciements Ce travail a été réalisé au Laboratoire de Biochimie Cellulaire et Moléculaire, USTHB, avec l’équipe de Biochimie -Biomolécules, Mode d’action - Diagnostique et Immunothèrapie, ainsi qu’au Laboratoire d’Eco -epidémiologie Parasitaire et Génetique des Population, Institut Pasteur d’Algérie. En premier lieu, je tiens à exprimer ma gratitude à Madame le Professeur Fatima LARABA-DJEBARI, chef de l’équipe Biochimie-Biomolécules, Mode d’action - Diagnostic et Immunothèrapie , pour m’avoir accueillie dans son équipe et accepté de présider le jury de thèse. Je vous remercie, pour votre contribution à ce travail, votre rigueur scientifique, vos intarissables conseils et votre soutien. Je souhaite également remercier ma directrice de thèse, Madame le Professeur Habiba OUSSEDIK-OUMEHDI, qui a dirigé et encadré ce travail. Je vous remercie particulièrement pour votre confiance et votre patiente. Vous avez su me faire profiter de votre savoir, et de plus, apporté des critiques constructives pour me faire aller de l’avant et orienter mes recherches dans la bonne direction. Tout en étant attentive et généreuse en bons conseils, vous avez s u m’encourager dans les moments difficiles. J’adresse aussi toute ma reconnaissance au Professeur Zoubir HARRAT pour m’avoir accueilli au sein du Laboratoire d’Eco -epidémiologie Parasitaire et Génetique des Population, et qui nous fait honneur en prenant part au jury de thèse. Je le remercie d’avoir mis à ma disposition tous les moyens nécessaires pour le bon déroulement du travail. J’ai vraiment beaucoup appris au sein de son laboratoire autant sur le plan scientifique ou personnel. Certaines parties de ce travail ont été effectuées en collaboration avec l’équipe de la plateforme de Protéomique du Centre de Recherche Inserm (CRI) de l'Institut Albert Bonniot (Université J. Fourier - Grenoble). Je remercie vivement son directeur le Pr Michel SEVE de m’avoir accueilli, ainsi que son équipe, en particulier Sylvie MICHELLAND. Je les remercie pour leurs conseils, leur expertise technique et scientifique. J’adresse mes sincères remerciements aux membres du jury pour l’honneur qu’ils me font en ayant cordialement accepté d’examiner et d’expertiser ce travail. J’adresse également mes chaleureux remerciements au Professeur Abderrahmen MATI pour son amabilité et pour l’honneur qu’il nous fait d’avoir s i gentiment accepté de i participer à ce jury de thèse pour examiner ce travail. Veuillez trouver ici, l’expression de mes remerciements les plus sincères. Un grand merci à Madame le Docteur Hinda BOUKHALFA-ABIB pour son amabilité, ses encouragements et pour l’honneur qu’elle nous fait d’avoir accepté d’examiner ce travail. Veuillez trouver ici, mes sincères remerciements. Mes vifs remerciements au Docteur Fatah CHERIFI pour son amabilité, ses conseils pertinents et pour l’honneur qu’il nous fait pour examiner ce travail. Veuillez trouver ici, l’expression de mon profond respect. J’exprime ma pr ofonde gratitude au Professeur Rachid AMIROUCHE du Laboratoire de Biologie et Physiologie des Organismes pour avoir mis à notre disposition le microscope à fluorescence. Aussi, je remercie le Pr Ghania HARITI, chef de service Hémobiologie, du CHU de Bab El Oued pour nous avoir accordé, avec amabilité, de faire l’analyse d’agrégation plaquettaire. Je tiens à remercier tous mes collègues du laboratoire de Biochimie Cellulaire et Moléculaire et tous mes enseignants de graduation. Je tiens particulièrement à remercier mes très chères amies: Hadjer, Dalila, Louiza, Khedidja, Zola, Asma, Meriem, Chanez, Imene, Nesrine, Nasrine, Amina et Yasmine pour leur accompagnement durant ces années de thèse. Ils ont su insuffler une ambiance, fort chaleureuse, et grâce à eux j’ai passé d’agréables moments. J’associe à ces remerciements les ingénieurs du laboratoire, Manel, Samia et Khaoula et tout le personnel de la FSB-USTHB. Je remercie également toutes les personnes que j’ai pu côtoyer à l’IPA ; en particulier Ghania MEZAI, je la remercie pour sa bonne humeur et ses précieux conseils. Je remercie de même le Docteur Naouel EDDAIKRA pour ces orientations techniques et scientifiques.Je n’oublierais pas pour autant, Ihcen KHERACHI, Sihem BENBETKA, Rafik GARNI, Adlene vous formez une merveilleuse équipe. Merci également à Sandrine Bourgoin-Voillard, Valerie CUNIN de l’équipe de la plateforme de protéomique . ii J’adresse t out particulièrement, mes vifs remerciements à mes parents. Je vous remercie pour votre soutien indéfectible, votre patience durant ces années de thèse. À mon frère Dahmane et son épouse Nesrine. À mon petit frère Yacine. À mes adorables cousines Kahina, Fariza et Katia. À mes très cheres amies; Chahrazed, Meriem et Fouzia , mes trois ID, avec qui j’ai partagé des moments inoubliables. Enfin, je dédie ce travail, à la mémoire de mes grands-parents, que dieu les accueille dans son vaste paradis. iii « La science ne résout jamais un problème sans en créer dix autres » George Bernard Shaw Table des matières Remerciements ............................................................................................................................. i Liste des abréviations ................................................................................................................. vi INTRODUCTION ....................................................................................................................... 1 I. REVUE BIBLIOGRAPHIQUE .......................................................................................... 4 I.1. Composition des venins vipérins .......................................................................................... 4 I.1.1. Les enzymes ....................................................................................................................... 4 I.1.1.1. Les sérine-protéinases ..................................................................................................... 4 I.1.1.2. Les métalloprotéinases .................................................................................................... 5 I.1.1.3. Les hyaluronidases .......................................................................................................... 9 I.1.1.4. Les L- amino acide oxydases .......................................................................................... 9 I.1.1.5. Les phospholipases A2 ................................................................................................. 10 I.1.1.6. Les nucléotidases .......................................................................................................... 11 I.1.2. Les protéines non enzymatiques ...................................................................................... 11 I.1.2.1. Les myotoxines ............................................................................................................. 13 I.1.2.2. Les désintégrines ........................................................................................................... 13 I.1.2.3. Les lectine de type-C..................................................................................................... 14 I.1.2.4. Les protéines sécrétoires riches en cystéines ................................................................ 17 I.1.2.5. Les toxines à trois doigts ............................................................................................... 17 I.1.2.6. Les protéines de type Kunitz ......................................................................................... 18 I.2. Applications biotechnologiques et pharmacologiques des venins de serpents ................ 18 I.2.1. Biomolécules agissant sur le système cardiovasculaire ................................................... 18 I.2.2. Biomolécules agissant sur l'hémostase ............................................................................ 19 I.2.3. Biomolécules agissant sur la réponse inflammatoire ....................................................... 20 I.2.4. Biomolécules agissant sur le système immunitaire ......................................................... 21 I.2.5. Biomolécules avec activité cytotoxique et antitumorale ................................................. 21 I.2.6. Biomolécules avec activité antimicrobienne ................................................................... 22 I.3. Le venin de Cerastes cerastes ......................................................................................... 28 I.4. Généralités sur la leishmaniose .......................................................................................
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