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Oxidative stress in the skin barrier: Implications for stratum corneum antioxidants
031 PHOTOBIOLOGICAL AND MOLECULAR MECHANISMS OF ULTRAVIOLET A RADIATIONINDUCED GENE EXPRESSION IN HUMAN KERATINOCYTES S. Grether-Beck and J. Krutmann, Clinical & ExperimentalPhotodermatology, Dept of Dermatology,
OVERVIEW OF NATRIURETIC PEPTIDES (NP) Adolf0 J. de Bold Universityof OttawaHeart Irwtitute,Ottawa,Ontario,Canada Interference with the actions of NP impairs the ability of the cardiorenal axis to compensate during departures from homeostasis. Hence, understanding the control of production of these peptides is important in pathophysiological states. In vitro studies on cardiac ANF and BNP gene expression have shown that transcriptional activation proceding increased expression of each NP gene. These experiments also suggest that a cpmbination of stimuli may be necessary to maintain the increased expression of the cardiac NP genes observed in many cardiac pathologies. In vivo the ventricular reexpression of fetal isoforms of several cardiac proteins, including ANF and BNP, are hallmarks of the hypertrophic process. Under experimental conditions, however, one can dissociate anatomical hypertrophy from isoforrn switxh and increased NP gene expression. In addition, it is possible to differentiate a load-dependent from a load-independent component affecting NP gene expression during the development of ventricular hypertrophy. Recent studies indicate that the expression of NP genes is controlled by processes that are tissue-specific. DOCA-salt treatment, for example, upregulates cardiac ANF gene expression but it downregulates renal ANF gene expression. High renin states, on the other hand, tend to upregulate both renal and cardiac ANF gene expression. On the whole, new understanding has been gained recently regarding the regulation of NP production and its relevance in the pathophysiological state despite the realization that NP production control is a very complex issue.
Heinrich-Heine-University
Dusseldorf;
Germany
Increased gene expression as a consequence of environmental stress is typically observed in mammalian cells upon exposure to ultraviolet (UV) radiation. ln previous years the cis- and transacting genetic elements responsible for gene induction by shortwavelength UVC (< 280 nm) and intermediate wavelength UVB (280-320 nm) radiation have been well characterized. More recently, progress has also been made in understanding the mechanisms by which longwavelength UVA (320-400 nm) radiation induces transcriptional activation of genes in human keratinocytes. From these studies it is known that the photobiological as well as the molecular mechanisms involved in UVA radiation- induced expression of the adhesion molecule intercellular adhesion molecule-l (ICAM-I) differ from these relevant for UVB-induced ICAM1 expression. In particular, the reactive oxygen species singlet oxygen was found to serve as the primary effector in UVA radiation-induced ICAMexpression by inducing a signal transduction cascade which depends on activation or transcription factor AP-2. Recent studies indicate that ceramides which are released in UVA irradiated keratinocytes at increased amounts serve a pivotal role as second messenger in UVA radiation-induced, AP2-mediated ICAMgene expression. These studies indicate a previously unrecognized role of AP-2 in the regulation of immunologically relevant genes in human keratinocytes. OXIDATIVE STRESS IN THE SKIN BARRIER: IMPLICATIONS FOR STRATUM CORNEUM ANTIOXIDANTS Jens J. Thiele Heinrich-Heine-University, DuesseldorJ Germany
IMPLICATION OF BNP IN CARDIOVASCULAR PATHOPHYSIOLOGY - LESSONS FROM BNP TRANSGENIC AND KNOCKOUT MICE K. Nakao Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine Kyoto, Japan
As the outermost skin layer and penetration barrier of the body, the stratum comeum (SC) is frequently and directly exposed to a pro-oxrdative environment, including ultraviolet solar radiation (UVB and UVA), air pollutants (such as ozone), and chemicals. Therefore, we sought to investigate the physiological antioxidant gradients in SC and their sensitivity upon various types of oxidant exposures: a) ozone, b) UVB and UVA, and c) chemical oxidants. To test this, methods were developed to measure the lipophilic antioxidants vitamin E and coenzyme Q, the hydrophilic antioxidants vitamin C and urate, and the lipid peroxidation product malondialdehyde (MDA) in tape stripped SC. SKH-I hairless mice were exposed to various levels of ozone and solar simulated UVA and UVB radiation; furthermore, baseline levels of SC antioxidants were evaluated in human volunteers. Both in mice and humans, the SC contained unique antioxidant distribution gradients. Tocopherol, the major vitamin E homologue appears to be the predominating SC antioxidant with respect to its concentration and its unique susceptibility to the various oxidative challenges tested. Depletion of barrier tocopherols represent an early may pathophysiological event leading to the initiation of barrier disruption and inflammation in environmentally damaged skin.
The natriuretic peptide family consists of ANP, BNP and CNP. ANP is a cardiac hormone produced by the atrium. BNP first isolated from the brain is now known to be a cardiac hormone produced by the ventricle of the heart. CNP is the main natriuretic peptide in the central nervous system and is also produced by vascular endothelial cells and macrophages, indicating that CNP is a local regulator rather than a circulating hormone. In order to elucidate the implication of BNP in cardiovascular pathophysiology, we have succeeded in developing BNP transgenic and knockout mice. In the present paper, I will discuss lessons from phenotypes of BNP transgenic and knockout mice.
187
OVERVIEW OF NATRIURETIC PEPTIDES (NP) Adolf0 J. de Bold Universityof OttawaHeart Irwtitute,Ottawa,Ontario,Canada Interference with the actions of NP impairs the ability of the cardiorenal axis to compensate during departures from homeostasis. Hence, understanding the control of production of these peptides is important in pathophysiological states. In vitro studies on cardiac ANF and BNP gene expression have shown that transcriptional activation proceding increased expression of each NP gene. These experiments also suggest that a cpmbination of stimuli may be necessary to maintain the increased expression of the cardiac NP genes observed in many cardiac pathologies. In vivo the ventricular reexpression of fetal isoforms of several cardiac proteins, including ANF and BNP, are hallmarks of the hypertrophic process. Under experimental conditions, however, one can dissociate anatomical hypertrophy from isoforrn switxh and increased NP gene expression. In addition, it is possible to differentiate a load-dependent from a load-independent component affecting NP gene expression during the development of ventricular hypertrophy. Recent studies indicate that the expression of NP genes is controlled by processes that are tissue-specific. DOCA-salt treatment, for example, upregulates cardiac ANF gene expression but it downregulates renal ANF gene expression. High renin states, on the other hand, tend to upregulate both renal and cardiac ANF gene expression. On the whole, new understanding has been gained recently regarding the regulation of NP production and its relevance in the pathophysiological state despite the realization that NP production control is a very complex issue.
Heinrich-Heine-University
Dusseldorf;
Germany
Increased gene expression as a consequence of environmental stress is typically observed in mammalian cells upon exposure to ultraviolet (UV) radiation. ln previous years the cis- and transacting genetic elements responsible for gene induction by shortwavelength UVC (< 280 nm) and intermediate wavelength UVB (280-320 nm) radiation have been well characterized. More recently, progress has also been made in understanding the mechanisms by which longwavelength UVA (320-400 nm) radiation induces transcriptional activation of genes in human keratinocytes. From these studies it is known that the photobiological as well as the molecular mechanisms involved in UVA radiation- induced expression of the adhesion molecule intercellular adhesion molecule-l (ICAM-I) differ from these relevant for UVB-induced ICAM1 expression. In particular, the reactive oxygen species singlet oxygen was found to serve as the primary effector in UVA radiation-induced ICAMexpression by inducing a signal transduction cascade which depends on activation or transcription factor AP-2. Recent studies indicate that ceramides which are released in UVA irradiated keratinocytes at increased amounts serve a pivotal role as second messenger in UVA radiation-induced, AP2-mediated ICAMgene expression. These studies indicate a previously unrecognized role of AP-2 in the regulation of immunologically relevant genes in human keratinocytes. OXIDATIVE STRESS IN THE SKIN BARRIER: IMPLICATIONS FOR STRATUM CORNEUM ANTIOXIDANTS Jens J. Thiele Heinrich-Heine-University, DuesseldorJ Germany
IMPLICATION OF BNP IN CARDIOVASCULAR PATHOPHYSIOLOGY - LESSONS FROM BNP TRANSGENIC AND KNOCKOUT MICE K. Nakao Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine Kyoto, Japan
As the outermost skin layer and penetration barrier of the body, the stratum comeum (SC) is frequently and directly exposed to a pro-oxrdative environment, including ultraviolet solar radiation (UVB and UVA), air pollutants (such as ozone), and chemicals. Therefore, we sought to investigate the physiological antioxidant gradients in SC and their sensitivity upon various types of oxidant exposures: a) ozone, b) UVB and UVA, and c) chemical oxidants. To test this, methods were developed to measure the lipophilic antioxidants vitamin E and coenzyme Q, the hydrophilic antioxidants vitamin C and urate, and the lipid peroxidation product malondialdehyde (MDA) in tape stripped SC. SKH-I hairless mice were exposed to various levels of ozone and solar simulated UVA and UVB radiation; furthermore, baseline levels of SC antioxidants were evaluated in human volunteers. Both in mice and humans, the SC contained unique antioxidant distribution gradients. Tocopherol, the major vitamin E homologue appears to be the predominating SC antioxidant with respect to its concentration and its unique susceptibility to the various oxidative challenges tested. Depletion of barrier tocopherols represent an early may pathophysiological event leading to the initiation of barrier disruption and inflammation in environmentally damaged skin.
The natriuretic peptide family consists of ANP, BNP and CNP. ANP is a cardiac hormone produced by the atrium. BNP first isolated from the brain is now known to be a cardiac hormone produced by the ventricle of the heart. CNP is the main natriuretic peptide in the central nervous system and is also produced by vascular endothelial cells and macrophages, indicating that CNP is a local regulator rather than a circulating hormone. In order to elucidate the implication of BNP in cardiovascular pathophysiology, we have succeeded in developing BNP transgenic and knockout mice. In the present paper, I will discuss lessons from phenotypes of BNP transgenic and knockout mice.
187