Biochemical and Biological Effects of Organotins

Mechanisms of Organotin-Induced Apoptosis

Author(s): Zeljko Jaksic

Pp: 149-163 (15)

DOI: 10.2174/978160805265311201010149

* (Excluding Mailing and Handling)

Abstract

Apoptosis, a specific type of programmed cell death, is characterized by cell shrinkage, nucleus condensation and fragmentation, plasma membrane blebbing and final engulfment by neighboring cells or professional phagocytes. The molecular mechanisms of organotin-induced apoptosis, which involve a series of biochemical regulators and molecular interactions, have been extensively studied in different cell types but the apoptotic pathway mechanisms and signaling still remain unexplained in some detail. Apoptosis may be triggered and modulated by caspase-independent, and more frequently by caspase-dependent pathways. Pro-caspase activation is driven by death receptors, and/or by a mitochondrion-mediated mechanism. Although both pathways were described, the mitochondrial mechanism seems to be the most important one in organotin-induced apoptosis. Organotin compounds trigger cytoskeletal modifications and disruption of mitochondrial functions. Generally, the apoptotic pathway induced by organotins starts with their interactions with cellular components leading to perturbation of intracellular Ca2+ homeostasis, the latter especially triggered by endoplasmic reticulum stress, and intracellular Ca2+ concentration increase, cessation of ATP and reactive oxygen species production and loss of mitochondrial membrane potential. These events are followed by cytochrome c release from mitochondria to cytosol, apoptosome formation and final executioner caspase activation. The increase in intracellular Ca2+ level and the consequent mitochondrial cytochrome c release play critical steps in organotin-induced apoptosis. The process not only depends on cell type and sensitivity but also on organotin chemical characteristics and insult intensity. New and promising research on mechanisms of organotin-induced apoptosis is focused on the characterization of organotin interactions with apoptosis-related proteins and regulation of gene expression.


Keywords: Apoptosis - organotin-caspase modulation - endoplasmic reticulum stress - intracellular (Ca2+)- oxidative stress - mitochondria - MAP-kinase.

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      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 309684047 and j.to_ip >=309684047 )) and ((j.from_date <= 1739988052 and j.to_date >= 1739988052 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 58) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 309684047 and j.to_ip >=309684047 )) and ((j.from_date <= 1739988052 and j.to_date >= 1739988052 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 58) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 309684047 and j.to_ip >=309684047 )) and ((j.from_date <= 1739988052 and j.to_date >= 1739988052 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 58)
      630μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 797 and `b`.`banner_from_date` <= 1739988052 and `b`.`banner_to_date` >= 1739988052 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.04msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 797
      • 3: 1739988052
      • 4: 1739988052
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='80273f2597ea90c0ae2a06ce00265fb9'
      200μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Keywords
    1Keywords.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        qXZVWDf21SPi5rKETAUt8ra9FWT8PVrPILyCWAau
        uc_cart_id
        80273f2597ea90c0ae2a06ce00265fb9
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/chapter/58" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/58
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
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        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        response_headers
        0 of 0
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        session_attributes
        0 of 0
        array:5 [ "_token" => "qXZVWDf21SPi5rKETAUt8ra9FWT8PVrPILyCWAau" "uc_cart_id" => "80273f2597ea90c0ae2a06ce00265fb9" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/chapter/58" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-19 18:00:52GET/chapter/58112193